Most aspects of cellular events are regulated by a series of protein phosphorylation
and dephosphorylation processes. Abi (Abl interactor protein) functions as a substrate
adaptor protein for Abl and a core member of the WAVE complex, relaying signals
from Rac to Arp2/3 complex and regulating actin dynamics. It is known that the
recruitment of Abi into the lamella promotes polymerization of actin, although how it
does is still unclear. In this study, we found PTP61F, a Drosophila homolog of
mammalian PTP1B, can reverse the Abl phosphorylation of Abi and colocalizes with
Abi in Drosophila S2 cells. Abi can be translocalized from the cytosol to the cell
membrane by either increasing Abl or reducing endogenous PTP61F. This reciprocal
regulation of Abi phosphorylation is also involved in modulating Abi protein level,
which is thought to affect the stability of the WAVE complex. Using mass spectrometry,
we identified several important tyrosine phosphorylation sites in Abi. We compared the
translocalization and protein half-life of wild type (wt) and phosphomutant Abi and
their abilities to restore the lamellipodia structure of the Abi-reduced cells. We found
the phosphomutant to have reduced ability to translocalize and to have a protein
half-life shorter than that of wt Abi. We also found that although the wt Abi could fully
restore the lamellipodia structure, the phosphomutant could not. Together, these
findings suggest that the reciprocal regulation of Abi phosphorylation by Abl and
PTP61F may regulate the localization and stability of Abi and may regulate the
formation of lamella.
Actin polymerization is a key process for many cellular events during development.
During Drosophila neuronal development, Abl is involved in signalling pathway
regulating proper axon guidance of CNS and motor neurons. However, how Abi
integrate in Abl signalling during neuronal development is largely unknown. In this
study, we isolate several loss-of-function mutations in the Abi gene and carry out a
genetic analysis to test the genetic interaction between Abl and Abi. Reduction of Abi
gene dose by half results in suppression of lethality induced by Abl mutation implying
that Abi might be a genetic suppressor for Abl. Decrease Abi dose leads to embryonic
central nervous system development defects and attenuates Abl midline axon guidance
defects. In addition to axon guidance deficits, Abl mutation show defects in synapse
development on neuromuscular junction. Loss of Abl cause synaptic overgrowth and
2
increase of spontaneous synaptic transmission. Furthermore, these synaptic defects
could be alleviated by reducing Abi and Ena gene dose in Abl mutant animals. To
elucidate the relationship between Abl, Abi and Ena observed in genetic study, we
performed biochemical and cell biological analysis. Results revealed that Abi can
enhance the Abl-Ena association and recruit Abl to Ena. These observations suggest
actin associated protein Abi and Ena are integrated in Abl-mediated signaling networks
regulating neuronal axon guidance and synapse development.

細胞內大多數的功能是需要經由一連串蛋白質磷酸化及去磷酸作用而調節。
Abl 結合蛋白(Abi)是Abl 激脢的受質，並且在WAVE 複合蛋白體中扮演重要角色，
負責將訊息由Rac 傳至Arp2/3 複合蛋白，進而調控肌動蛋白的聚合。過去的研究
已知Abi 聚集至細胞邊緣能促進肌動蛋白的聚合，但是其機制仍不清楚。在本研
究中，我們發現PTP61F (哺乳類PTP1B 的同源蛋白)能夠反向調控Abl 對Abi 的磷
酸化作用並且影響Abi 在S2 細胞中的位置，在細胞中增加Abl 或移除PTP61F 的
表現會使Abi 移動至細胞邊緣。同時，Abi 的磷酸化調節也會影響Abi 在細胞中的
含量，進而可能影響WAVE 複合蛋白體中其他蛋白質的穩定性。我們利用質譜儀
分析鑑定，發現幾個Abi 被磷酸化的位置，並將這幾個位置進行定位點突變。進
一步分析突變型Abi 在細胞中移動的能力及穩定性，我們發現突變型Abi 在細胞
中移動的能力較差，並且蛋白質的半衰期較野生型短。另外，送回突變型Abi 也
無法回復去除Abi 所造成的lamella 形成缺失。總結來說，Abi 的磷酸化在Abl 及
PTP61F 的相互調節之下，會進一步影響Abi 在細胞中的位置、蛋白質的穩定性及
lamella 形成的功能。
在許多生物體發育的過程中，肌動蛋白的聚合扮演非常關鍵的步驟。在果蠅
的神經發育過程中，Abl 已知在神經軸突及運動神經元的前進引導上扮演重要功
能，但是Abi 如何參與在Abl 下游訊息傳遞路徑，並且影響神經系統的發育，其
機制仍不清楚。在本研究中，我們分離了數個Abi 果蠅突變株，並且藉由遺傳方
法的分析，進一步了解Abi 與Abl 的遺傳交互作用。由結果發現，降低Abi 的量
能夠回復Abl 突變所造成的成蟲死亡率，因此我們認為Abi 可能是Abl 在遺傳學
上的拮抗者。另外，Abi 的突變株果蠅除了其胚胎會有中樞神經系統發育的缺陷，
降低Abi 的量也能降低Abl 突變果蠅胚胎神經發育的缺陷。除了中樞神經系統的
發育，在本研究中我們也發現Abl 突變果蠅會出現神經肌肉接合處突觸發育的缺
陷。Abl 突變果蠅的突觸會過度生長並且自發性的神經傳導也有顯著的增加。更進
一步的研究發現，Abl 突變果蠅突觸的過度生長會經由降低Abi 及Ena 的量而減
緩。在生化及細胞生物學的分析中，Abi 被發現能夠促進Abl 及Ena 的結合，並且
改變Abl 在細胞中的分佈進而和Ena 結合。總結來說，Abi 和Ena 這兩個與肌動蛋
4
白有關的蛋白會參與在Abl 下游訊息傳遞網路，並且一同調控神經軸突前進引導
及突觸的發育。

Anderie, I., Schulz, I., and Schmid, A. (2007). Direct interaction between ER
membrane-bound PTP1B and its plasma membrane-anchored targets. Cell
Signal 19, 582-92.
Baeg, G. H., Zhou, R., and Perrimon, N. (2005). Genome-wide RNAi analysis of
JAK/STAT signaling components in Drosophila. Genes Dev 19, 1861-70.
Bashaw, G. J., Kidd, T., Murray, D., Pawson, T., and Goodman, C. S. (2000). Repulsive
axon guidance: Abelson and Enabled play opposing roles downstream of the
roundabout receptor. Cell 101, 703-15.
Bellen, H. J., and Budnik, V. (2000). The neuromuscular junction. In "Drosophila
Protocols", pp. 175-199. CSHL Press, Cold Spring Harbor, New York.
Ben-Yaacov, S., Le Borgne, R., Abramson, I., Schweisguth, F., and Schejter, E. D.
(2001). Wasp, the Drosophila Wiskott-Aldrich syndrome gene homologue, is
required for cell fate decisions mediated by Notch signaling. J Cell Biol 152,
1-13.
Bennett, R. L., and Hoffmann, F. M. (1992). Increased levels of the Drosophila Abelson
tyrosine kinase in nerves and muscles: subcellular localization and mutant
phenotypes imply a role in cell-cell interactions. Development 116, 953-66.
Blanchetot, C., Chagnon, M., Dube, N., Halle, M., and Tremblay, M. L. (2005).
Substrate-trapping techniques in the identification of cellular PTP targets.
Methods 35, 44-53.
Bogdan, S., Grewe, O., Strunk, M., Mertens, A., and Klambt, C. (2004). Sra-1 interacts
with Kette and Wasp and is required for neuronal and bristle development in
Drosophila. Development 131, 3981-9.
Bogdan, S., and Klambt, C. (2003). Kette regulates actin dynamics and genetically
interacts with Wave and Wasp. Development 130, 4427-37.
Bogdan, S., Stephan, R., Lobke, C., Mertens, A., and Klambt, C. (2005). Abi activates
WASP to promote sensory organ development. Nat Cell Biol 7, 977-84.
Breen, T. R., and Harte, P. J. (1991). Molecular characterization of the trithorax gene, a
positive regulator of homeotic gene expression in Drosophila. Mech Dev 35,
113-27.
Cherezova, L., Gatesman, A., and Flynn, D. C. (2002). The effects of phosphorylation
46
on adaptor protein function. Front Biosci 7, d164-203.
Chou, T. B., and Perrimon, N. (1996). The autosomal FLP-DFS technique for
generating germline mosaics in Drosophila melanogaster. Genetics 144, 1673-9.
Clemens, J. C., Ursuliak, Z., Clemens, K. K., Price, J. V., and Dixon, J. E. (1996). A
Drosophila protein-tyrosine phosphatase associates with an adapter protein
required for axonal guidance. J Biol Chem 271, 17002-5.
Cohen, P. (1999). The development and therapeutic potential of protein kinase inhibitors.
Curr Opin Chem Biol 3, 459-65.
Cohen, P. (2000). The regulation of protein function by multisite phosphorylation--a 25
year update. Trends Biochem Sci 25, 596-601.
Courtney, K. D., Grove, M., Vandongen, H., Vandongen, A., LaMantia, A. S., and
Pendergast, A. M. (2000). Localization and phosphorylation of Abl-interactor
proteins, Abi-1 and Abi-2, in the developing nervous system. Mol Cell Neurosci
16, 244-57.
Cowan, C. A., and Henkemeyer, M. (2001). The SH2/SH3 adaptor Grb4 transduces
B-ephrin reverse signals. Nature 413, 174-9.
Coyle, I. P., Koh, Y. H., Lee, W. C., Slind, J., Fergestad, T., Littleton, J. T., and Ganetzky,
B. (2004). Nervous wreck, an SH3 adaptor protein that interacts with Wsp,
regulates synaptic growth in Drosophila. Neuron 41, 521-34.
Dai, Z., and Pendergast, A. M. (1995). Abi-2, a novel SH3-containing protein interacts
with the c-Abl tyrosine kinase and modulates c-Abl transforming activity. Genes
Dev 9, 2569-82.
Dai, Z., Quackenbush, R. C., Courtney, K. D., Grove, M., Cortez, D., Reuther, G. W.,
and Pendergast, A. M. (1998). Oncogenic Abl and Src tyrosine kinases elicit the
ubiquitin-dependent degradation of target proteins through a Ras-independent
pathway. Genes Dev 12, 1415-24.
Dent, E. W., and Gertler, F. B. (2003). Cytoskeletal dynamics and transport in growth
cone motility and axon guidance. Neuron 40, 209-27.
Dillon, C., and Goda, Y. (2005). The actin cytoskeleton: integrating form and function at
the synapse. Annu Rev Neurosci 28, 25-55.
Douziech, M., Roy, F., Laberge, G., Lefrancois, M., Armengod, A. V., and Therrien, M.
(2003). Bimodal regulation of RAF by CNK in Drosophila. Embo J 22, 5068-78.
Dube, N., and Tremblay, M. L. (2005). Involvement of the small protein tyrosine
phosphatases TC-PTP and PTP1B in signal transduction and diseases: from
47
diabetes, obesity to cell cycle, and cancer. Biochim Biophys Acta 1754, 108-17.
Eden, S., Rohatgi, R., Podtelejnikov, A. V., Mann, M., and Kirschner, M. W. (2002).
Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck.
Nature 418, 790-3.
Ensslen-Craig, S. E., and Brady-Kalnay, S. M. (2004). Receptor protein tyrosine
phosphatases regulate neural development and axon guidance. Dev Biol 275,
12-22.
Feng, Y., Ueda, A., and Wu, C. F. (2004). A modified minimal hemolymph-like solution,
HL3.1, for physiological recordings at the neuromuscular junctions of normal
and mutant Drosophila larvae. J Neurogenet 18, 377-402.
Finn, A. J., Feng, G., and Pendergast, A. M. (2003). Postsynaptic requirement for Abl
kinases in assembly of the neuromuscular junction. Nat Neurosci 6, 717-23.
Fogerty, F. J., Juang, J. L., Petersen, J., Clark, M. J., Hoffmann, F. M., and Mosher, D. F.
(1999). Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis.
Oncogene 18, 219-32.
Forsthoefel, D. J., Liebl, E. C., Kolodziej, P. A., and Seeger, M. A. (2005). The Abelson
tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor
Frazzled in Drosophila. Development 132, 1983-94.
Frangioni, J. V., Beahm, P. H., Shifrin, V., Jost, C. A., and Neel, B. G. (1992). The
nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic
reticulum via its 35 amino acid C-terminal sequence. Cell 68, 545-60.
Frangioni, J. V., Oda, A., Smith, M., Salzman, E. W., and Neel, B. G. (1993).
Calpain-catalyzed cleavage and subcellular relocation of protein
phosphotyrosine phosphatase 1B (PTP-1B) in human platelets. Embo J 12,
4843-56.
Gallo, G., and Letourneau, P. C. (2004). Regulation of growth cone actin filaments by
guidance cues. J Neurobiol 58, 92-102.
Gertler, F. B., Bennett, R. L., Clark, M. J., and Hoffmann, F. M. (1989). Drosophila abl
tyrosine kinase in embryonic CNS axons: a role in axonogenesis is revealed
through dosage-sensitive interactions with disabled. Cell 58, 103-13.
Gertler, F. B., Comer, A. R., Juang, J. L., Ahern, S. M., Clark, M. J., Liebl, E. C., and
Hoffmann, F. M. (1995). enabled, a dosage-sensitive suppressor of mutations in
the Drosophila Abl tyrosine kinase, encodes an Abl substrate with SH3
domain-binding properties. Genes Dev 9, 521-33.
48
Gertler, F. B., Doctor, J. S., and Hoffmann, F. M. (1990). Genetic suppression of
mutations in the Drosophila abl proto-oncogene homolog. Science 248, 857-60.
Gertler, F. B., Hill, K. K., Clark, M. J., and Hoffmann, F. M. (1993). Dosage-sensitive
modifiers of Drosophila abl tyrosine kinase function: prospero, a regulator of
axonal outgrowth, and disabled, a novel tyrosine kinase substrate. Genes Dev 7,
441-53.
Gong, W. J., and Golic, K. G. (2003). Ends-out, or replacement, gene targeting in
Drosophila. Proc Natl Acad Sci U S A 100, 2556-61.
Goshima, G., and Vale, R. D. (2005). Cell cycle-dependent dynamics and regulation of
mitotic kinesins in Drosophila S2 cells. Mol Biol Cell 16, 3896-907.
Gramates, L. S., and Budnik, V. (1999). Assembly and maturation of the Drosophila
larval neuromuscular junction. Int Rev Neurobiol 43, 93-117.
Grevengoed, E. E., Loureiro, J. J., Jesse, T. L., and Peifer, M. (2001). Abelson kinase
regulates epithelial morphogenesis in Drosophila. J Cell Biol 155, 1185-98.
Grove, M., Demyanenko, G., Echarri, A., Zipfel, P. A., Quiroz, M. E., Rodriguiz, R. M.,
Playford, M., Martensen, S. A., Robinson, M. R., Wetsel, W. C., Maness, P. F.,
and Pendergast, A. M. (2004). ABI2-deficient mice exhibit defective cell
migration, aberrant dendritic spine morphogenesis, and deficits in learning and
memory. Mol Cell Biol 24, 10905-22.
Haj, F. G., Verveer, P. J., Squire, A., Neel, B. G., and Bastiaens, P. I. (2002). Imaging
sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic
reticulum. Science 295, 1708-11.
Hantschel, O., Nagar, B., Guettler, S., Kretzschmar, J., Dorey, K., Kuriyan, J., and
Superti-Furga, G. (2003). A myristoyl/phosphotyrosine switch regulates c-Abl.
Cell 112, 845-57.
Head, J. A., Jiang, D., Li, M., Zorn, L. J., Schaefer, E. M., Parsons, J. T., and Weed, S. A.
(2003). Cortactin tyrosine phosphorylation requires Rac1 activity and
association with the cortical actin cytoskeleton. Mol Biol Cell 14, 3216-29.
Henkemeyer, M. J., Gertler, F. B., Goodman, W., and Hoffmann, F. M. (1987). The
Drosophila Abelson proto-oncogene homolog: identification of mutant alleles
that have pleiotropic effects late in development. Cell 51, 821-8.
Hill, K. K., Bedian, V., Juang, J. L., and Hoffmann, F. M. (1995). Genetic interactions
between the Drosophila Abelson (Abl) tyrosine kinase and failed axon
connections (fax), a novel protein in axon bundles. Genetics 141, 595-606.
49
Huang, C. H., Lin, T. Y., Pan, R. L., and Juang, J. L. (2007). The involvement of Abl
and PTP61F in the regulation of Abi protein localization and stability and
lamella formation in Drosophila S2 cells. J Biol Chem 282, 32442-52.
Hummel, T., Leifker, K., and Klambt, C. (2000). The Drosophila HEM-2/NAP1
homolog KETTE controls axonal pathfinding and cytoskeletal organization.
Genes Dev 14, 863-73.
Ibarra, N., Blagg, S. L., Vazquez, F., and Insall, R. H. (2006). Nap1 regulates
Dictyostelium cell motility and adhesion through SCAR-dependent and
-independent pathways. Curr Biol 16, 717-22.
Innocenti, M., Gerboth, S., Rottner, K., Lai, F. P., Hertzog, M., Stradal, T. E., Frittoli, E.,
Didry, D., Polo, S., Disanza, A., Benesch, S., Di Fiore, P. P., Carlier, M. F., and
Scita, G. (2005). Abi1 regulates the activity of N-WASP and WAVE in distinct
actin-based processes. Nat Cell Biol 7, 969-76.
Innocenti, M., Zucconi, A., Disanza, A., Frittoli, E., Areces, L. B., Steffen, A., Stradal, T.
E., Di Fiore, P. P., Carlier, M. F., and Scita, G. (2004). Abi1 is essential for the
formation and activation of a WAVE2 signalling complex. Nat Cell Biol 6,
319-27.
Jackson, P., and Baltimore, D. (1989). N-terminal mutations activate the leukemogenic
potential of the myristoylated form of c-abl. Embo J 8, 449-56.
Johnson, K. G., and Van Vactor, D. (2003). Receptor protein tyrosine phosphatases in
nervous system development. Physiol Rev 83, 1-24.
Juang, J. L., and Hoffmann, F. M. (1999). Drosophila abelson interacting protein (dAbi)
is a positive regulator of abelson tyrosine kinase activity. Oncogene 18, 5138-47.
Kao, H. H., and Yeh, S. R. (2008). Mutation of Drosophila Abl, Abi, or FAK alters
synaptic efficacy in larval neuromuscular junction. In "Institute of Molecular
Medicine". National Tsing Hua University, Hsinchu, Taiwan.
Kaufmann, N., DeProto, J., Ranjan, R., Wan, H., and Van Vactor, D. (2002). Drosophila
liprin-alpha and the receptor phosphatase Dlar control synapse morphogenesis.
Neuron 34, 27-38.
Koh, T. W., Korolchuk, V. I., Wairkar, Y. P., Jiao, W., Evergren, E., Pan, H., Zhou, Y.,
Venken, K. J., Shupliakov, O., Robinson, I. M., O'Kane, C. J., and Bellen, H. J.
(2007). Eps15 and Dap160 control synaptic vesicle membrane retrieval and
synapse development. J Cell Biol 178, 309-22.
Koh, T. W., Verstreken, P., and Bellen, H. J. (2004). Dap160/intersectin acts as a
50
stabilizing scaffold required for synaptic development and vesicle endocytosis.
Neuron 43, 193-205.
Koleske, A. J., Gifford, A. M., Scott, M. L., Nee, M., Bronson, R. T., Miczek, K. A., and
Baltimore, D. (1998). Essential roles for the Abl and Arg tyrosine kinases in
neurulation. Neuron 21, 1259-72.
Krause, M., Dent, E. W., Bear, J. E., Loureiro, J. J., and Gertler, F. B. (2003). Ena/VASP
proteins: regulators of the actin cytoskeleton and cell migration. Annu Rev Cell
Dev Biol 19, 541-64.
Kruh, G. D., Perego, R., Miki, T., and Aaronson, S. A. (1990). The complete coding
sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases.
Proc Natl Acad Sci U S A 87, 5802-6.
Kunda, P., Craig, G., Dominguez, V., and Baum, B. (2003). Abi, Sra1, and Kette control
the stability and localization of SCAR/WAVE to regulate the formation of
actin-based protrusions. Curr Biol 13, 1867-75.
Lanier, L. M., and Gertler, F. B. (2000). From Abl to actin: Abl tyrosine kinase and
associated proteins in growth cone motility. Curr Opin Neurobiol 10, 80-7.
Lee, D. Y., Cho, H. I., Kang, Y. H., Yun, S. S., Park, S. Y., Lee, Y. S., Kim, Y., and Lee,
D. S. (2004a). The role of fluorescence in situ hybridization (FISH) for
monitoring hematologic malignancies with BCR/ABL or ETO/AML1
rearrangement: a comparative study with FISH and G-banding on 919
consecutive specimens of hematologic malignancies. Cancer Genet Cytogenet
152, 1-7.
Lee, H., Engel, U., Rusch, J., Scherrer, S., Sheard, K., and Van Vactor, D. (2004b). The
microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of
the tyrosine kinase Abl in mediating axon guidance. Neuron 42, 913-26.
Leng, Y., Zhang, J., Badour, K., Arpaia, E., Freeman, S., Cheung, P., Siu, M., and
Siminovitch, K. (2005). Abelson-interactor-1 promotes WAVE2 membrane
translocation and Abelson-mediated tyrosine phosphorylation required for
WAVE2 activation. Proc Natl Acad Sci U S A 102, 1098-103.
Li, W., Li, Y., and Gao, F. B. (2005). Abelson, enabled, and p120 catenin exert distinct
effects on dendritic morphogenesis in Drosophila. Dev Dyn 234, 512-22.
Liebl, E. C., Forsthoefel, D. J., Franco, L. S., Sample, S. H., Hess, J. E., Cowger, J. A.,
Chandler, M. P., Shupert, A. M., and Seeger, M. A. (2000). Dosage-sensitive,
reciprocal genetic interactions between the Abl tyrosine kinase and the putative
51
GEF trio reveal trio's role in axon pathfinding. Neuron 26, 107-18.
Lin, H., Lin, T. Y., and Juang, J. L. (2007). Abl deregulates Cdk5 kinase activity and
subcellular localization in Drosophila neurodegeneration. Cell Death Differ 14,
607-15.
Lin, T. Y., Huang, C. H., Chou, W. G., and Juang, J. L. (2004). Abi enhances
Abl-mediated CDC2 phosphorylation and inactivation. J Biomed Sci 11, 902-10.
Marrus, S. B., and DiAntonio, A. (2004). Preferential localization of glutamate
receptors opposite sites of high presynaptic release. Curr Biol 14, 924-31.
Martin, M., Ahern-Djamali, S. M., Hoffmann, F. M., and Saxton, W. M. (2005). Abl
tyrosine kinase and its substrate Ena/VASP have functional interactions with
kinesin-1. Mol Biol Cell 16, 4225-30.
Maruoka, M., Suzuki, J., Kawata, S., Yoshida, K., Hirao, N., Sato, S., Goff, S. P.,
Takeya, T., Tani, K., and Shishido, T. (2005). Identification of B cell adaptor for
PI3-kinase (BCAP) as an Abl interactor 1-regulated substrate of Abl kinases.
FEBS Lett 579, 2986-90.
Moresco, E. M., and Koleske, A. J. (2003). Regulation of neuronal morphogenesis and
synaptic function by Abl family kinases. Curr Opin Neurobiol 13, 535-44.
Moresco, E. M., Scheetz, A. J., Bornmann, W. G., Koleske, A. J., and Fitzsimonds, R. M.
(2003). Abl family nonreceptor tyrosine kinases modulate short-term synaptic
plasticity. J Neurophysiol 89, 1678-87.
Nolz, J. C., Gomez, T. S., Zhu, P., Li, S., Medeiros, R. B., Shimizu, Y., Burkhardt, J. K.,
Freedman, B. D., and Billadeau, D. D. (2006). The WAVE2 complex regulates
actin cytoskeletal reorganization and CRAC-mediated calcium entry during T
cell activation. Curr Biol 16, 24-34.
Patel, N. H., Snow, P. M., and Goodman, C. S. (1987). Characterization and cloning of
fasciclin III: a glycoprotein expressed on a subset of neurons and axon pathways
in Drosophila. Cell 48, 975-88.
Proepper, C., Johannsen, S., Liebau, S., Dahl, J., Vaida, B., Bockmann, J., Kreutz, M. R.,
Gundelfinger, E. D., and Boeckers, T. M. (2007). Abelson interacting protein 1
(Abi-1) is essential for dendrite morphogenesis and synapse formation. Embo J
26, 1397-409.
Ptacek, J., and Snyder, M. (2006). Charging it up: global analysis of protein
phosphorylation. Trends Genet 22, 545-54.
Qurashi, A., Sahin, H. B., Carrera, P., Gautreau, A., Schenck, A., and Giangrande, A.
52
(2007). HSPC300 and its role in neuronal connectivity. Neural Develop 2, 18.
Resh, M. D. (1999). Fatty acylation of proteins: new insights into membrane targeting
of myristoylated and palmitoylated proteins. Biochim Biophys Acta 1451, 1-16.
Roche, J. P., Packard, M. C., Moeckel-Cole, S., and Budnik, V. (2002). Regulation of
synaptic plasticity and synaptic vesicle dynamics by the PDZ protein Scribble. J
Neurosci 22, 6471-9.
Rogers, S. L., Wiedemann, U., Stuurman, N., and Vale, R. D. (2003). Molecular
requirements for actin-based lamella formation in Drosophila S2 cells. J Cell
Biol 162, 1079-88.
Sanchez-Soriano, N., Tear, G., Whitington, P., and Prokop, A. (2007). Drosophila as a
genetic and cellular model for studies on axonal growth. Neural Develop 2, 9.
Schenck, A., Bardoni, B., Langmann, C., Harden, N., Mandel, J. L., and Giangrande, A.
(2003). CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the
Rac1 GTPase pathway to the fragile X protein. Neuron 38, 887-98.
Schenck, A., Qurashi, A., Carrera, P., Bardoni, B., Diebold, C., Schejter, E., Mandel, J.
L., and Giangrande, A. (2004). WAVE/SCAR, a multifunctional complex
coordinating different aspects of neuronal connectivity. Dev Biol 274, 260-70.
Scita, G., Tenca, P., Areces, L. B., Tocchetti, A., Frittoli, E., Giardina, G., Ponzanelli, I.,
Sini, P., Innocenti, M., and Di Fiore, P. P. (2001). An effector region in Eps8 is
responsible for the activation of the Rac-specific GEF activity of Sos-1 and for
the proper localization of the Rac-based actin-polymerizing machine. J Cell Biol
154, 1031-44.
Shi, Y., Alin, K., and Goff, S. P. (1995). Abl-interactor-1, a novel SH3 protein binding to
the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming
activity. Genes Dev 9, 2583-97.
Smith, J. A., and Liebl, E. C. (2005). Identification of the molecular lesions in alleles of
the Drosophila Abelson tyrosine kinase. Drosophila Information Service 88,
20-22.
Steffen, A., Rottner, K., Ehinger, J., Innocenti, M., Scita, G., Wehland, J., and Stradal, T.
E. (2004). Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia
formation. Embo J 23, 749-59.
Stradal, T., Courtney, K. D., Rottner, K., Hahne, P., Small, J. V., and Pendergast, A. M.
(2001). The Abl interactor proteins localize to sites of actin polymerization at the
tips of lamellipodia and filopodia. Curr Biol 11, 891-5.
53
Stradal, T. E., Rottner, K., Disanza, A., Confalonieri, S., Innocenti, M., and Scita, G.
(2004). Regulation of actin dynamics by WASP and WAVE family proteins.
Trends Cell Biol 14, 303-11.
Stradal, T. E., and Scita, G. (2006). Protein complexes regulating Arp2/3-mediated actin
assembly. Curr Opin Cell Biol 18, 4-10.
Stuart, J. R., Gonzalez, F. H., Kawai, H., and Yuan, Z. M. (2006). c-Abl interacts with
the WAVE2 signaling complex to induce membrane ruffling and cell spreading.
J Biol Chem 281, 31290-7.
Suetsugu, S., Kurisu, S., Oikawa, T., Yamazaki, D., Oda, A., and Takenawa, T. (2006).
Optimization of WAVE2 complex-induced actin polymerization by
membrane-bound IRSp53, PIP(3), and Rac. J Cell Biol 173, 571-85.
Tani, K., Sato, S., Sukezane, T., Kojima, H., Hirose, H., Hanafusa, H., and Shishido, T.
(2003). Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian
enabled (Mena) by c-Abl kinase. J Biol Chem 278, 21685-92.
Van Etten, R. A. (1999). Cycling, stressed-out and nervous: cellular functions of c-Abl.
Trends Cell Biol 9, 179-86.
Wang, J. Y., Ledley, F., Goff, S., Lee, R., Groner, Y., and Baltimore, D. (1984). The
mouse c-abl locus: molecular cloning and characterization. Cell 36, 349-56.
Weiner, O. D., Rentel, M. C., Ott, A., Brown, G. E., Jedrychowski, M., Yaffe, M. B.,
Gygi, S. P., Cantley, L. C., Bourne, H. R., and Kirschner, M. W. (2006). Hem-1
complexes are essential for Rac activation, actin polymerization, and myosin
regulation during neutrophil chemotaxis. PLoS Biol 4, e38.
Wills, Z., Emerson, M., Rusch, J., Bikoff, J., Baum, B., Perrimon, N., and Van Vactor, D.
(2002). A Drosophila homolog of cyclase-associated proteins collaborates with
the Abl tyrosine kinase to control midline axon pathfinding. Neuron 36, 611-22.
Wills, Z., Marr, L., Zinn, K., Goodman, C. S., and Van Vactor, D. (1999). Profilin and
the Abl tyrosine kinase are required for motor axon outgrowth in the Drosophila
embryo. Neuron 22, 291-9.
Zhou, F. Q., and Cohan, C. S. (2004). How actin filaments and microtubules steer
growth cones to their targets. J Neurobiol 58, 84-91.