神經細胞是種高度特化的細胞，具有一軸突和多個樹突，分別負責訊號傳遞和訊號接收。細胞本體裡新合成的蛋白質會被打包成囊泡狀結構由分子馬達運輸至目的地。分子馬達kineisin和dynein負責胞內長途的運輸。然而分子馬達與貨物(突觸囊泡、RNA、粒線體等等)間的辨認和調控的機制仍有待研究。KIF1A/UNC-104 (kineisin)負責突觸囊泡運輸。近來研究顯示突觸前區域蛋白質Liprin-α/SYD-2可調控KIF1A/UNC-104在軸突上的聚集和運輸效率。KIF1A/UNC-104利用其C端的PH domain連接上突觸囊泡胞膜的脂質(PIP2)，我們假設此連接不足以提供分子馬達—貨物間的專一性辨識。另一突觸前區域蛋白質RIM/UNC-10的C端具有Liprin-α/SYD-2結合部位，N端可和Rab3/RAB-3結合。因此我們假設有另一連結(RAB-3—UNC-10—SYD-2) 可連接分子馬達和突觸囊泡。我們在ΔPH-UNC-104中研究是否除了PH domain以外還有其他和囊泡的連結，我們比較不同突觸囊泡標誌(SNB-1和RAB-3)和ΔPH-UNC-104間的螢光共位分析，結果顯示兩者的螢光共位分析並無差異。我們轉而比較RAB-3和SNB-1在syd-2 或unc-10突變株中的運輸，結果在syd-2突變株中SNB-1和RAB-3運輸皆受影響，而在unc-10突變株中僅RAB-3運輸有所影響而不影響SNB-1運輸，此結果指出我們所提出的連結(RAB-3—UNC-10—SYD-2)可能存在。

Neurons are specialized cells with an axon for signal conduction and transmission and dendrites for signal reception. Newly synthesized proteins in the cell body are packed into vesicular structures and are then transported by individual transporters to their destinations. Molecular motors as kinesins and dyneins are responsible for the long-range cargo (precursors, synaptic vesicles, mitochondria, RNA granules etc.) transport in neurons. Motor-cargo recognition and regulation of transport, however, remains broadly elusive. Kinesin-3 motor KIF1A/UNC-104 is responsible for synaptic vesicle precursor transport. Recent studies reveal that the pre-synaptic protein Liprin-α/SYD-2 regulates KIF1A/UNC-104 clustering along axons and motor transport efficiency. KIF1A/UNC-104 is known to attach to synaptic vesicles through a motor-lipid interaction. The C-terminal PH-domain of KIF1A/UNC-104 can specifically and directly bind to acidic phospholipids (PIP2), which are located in the vesicle membrane, and thereby connect the motor to the cargo. However, in this study we propose that the sole lipid-PH-domain interaction may not be sufficient for motor-cargo binding and recognition. Interestingly, RIM/UNC-10 reveals a binding site for Liprin-α/SYD-2 at the C-terminus while its N-terminus binds to Rab3/RAB-3. Therefore, we propose an additional linker RAB-3/UNC-10/SYD-2 for the UNC-104/vesicle interaction. Thus, we set out to investigate colocalization between UNC-104ΔPH::GFP and SNB-1::mRFP as well as UNC-104ΔPH::GFP and mCherry::RAB-3 to understand whether or not the additional linkage exists between UNC-104 and synaptic vesicle, and results revealed that there is no difference between RAB-3- or SNB-1-carrying vesicles. To understand the role of UNC-10 and SYD-2 on SNB-1 and RAB-3 vesicle transport, we monitored axonal trafficking using confocal spinning disk microscopy in C. elegans carrying unc-10 and syd-2 null mutations, and results revealed that both RAB-3 and SNB-1 trafficking were affected in syd-2 background, while in unc-10 mutants only RAB-3 trafficking was affected, and this may suggest that the proposed additional linkage RAB-3—UNC-10—SYD-2 may exist and help motor associate with its cargo.

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