| Autor: |
Bhan, Prerana, Bayansan, Odvogmed, Chang, Chien-Yu, Wagner, Oliver Ingvar |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| DOI: |
10.1101/723247 |
| Popis: |
KIF1A (UNC-104 in C. elegans ) is the major fast axonal transporter of STVs (synaptic vesicle protein transport vesicles) containing synaptic precursors such as RAB-3 or synaptobrevin-1 (SNB-1). Heritable mutations in neuronal motor proteins (and their adaptors) lead to numerous neurodegenerative diseases. The C-terminal PH (pleckstrin homolog) domain of UNC-104 directly binds to phosphatidylinositol 4,5-bisphosphate that form the lipid bilayers of STVs. Based on literature evidences, we hypothesize that RAB-3-bound STVs may employ a dual linker UNC-10/SYD-2 to connect to UNC-104. This RAB-3/UNC-10/SYD-2 linker may act as an additional reinforcement for the (supposed) weak motor-lipid interaction. Results from RT-PCR and Western blot experiments favor a genetic relation between SYD-2, UNC-10 and RAB-3, as well as co-immunoprecipitation assays revealed changes in binding affinities between SYD-2 and UNC-104 depending on the presence or absence of UNC-10 or RAB-3. Such changes in binding properties between SYD-2 and UNC-104 (depending on unc-10 and rab-3 ) can be also seen in colocalization and BiFC (bimolecular fluorescence complementation) assays. In sublateral neuronal bundles, as well as in single ALM mechanosensory neurons, UNC-104 expression appears to be more diffused and is restricted to short travel distances (with visibly reduced speeds) in unc-10 and rab-3 mutants. Similar results were revealed when observing RAB-3-containing vesicles but not synaptobrevin-1 (SNB-1)-containing vesicles. Moreover, deletion of UNC-104’s PH domain did not affect UNC-104/RAB-3 colocalization while it did affect UNC-104/SNB-1 colocalization. These findings solidly support the model a dual UNC-10/SYD-2 linker acting as a sufficient buttress to connect the motor to RAB-3-containing vesicles. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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