BAY-61-3606 Grabs Fully Free Turbo-Charge... By A Civic Project Group

In unc-13 mutants the BAR dispersion rate was?significantly decreased (WT �� = 32.3 �� 2.8 s, unc-13 ��?=?122.6 �� 16.7; p Thymidine kinase A66W and wild-type check details UNC-57 were indistinguishable and were slowed to the same extent in unc-13 mutants ( Figure?5C). Similarly, the dimerization defective UNC-57(��H1I) mutant was localized to presynaptic elements ( Figure?S6), and its dispersion rate was significantly reduced in unc-13 mutants (WT �� = 20.5 �� 2.5 s, unc-13 �� = 48.5 �� 5.2 s; p selleckchem faster than that observed for wild-type UNC-57 (Figure?5D), and the ��H1I synaptic enrichment was also reduced (Figure?S6B). These results suggest that monomeric UNC-57 binds to SVs with lower affinity than UNC-57 dimers. If UNC-57 binds directly to SVs, we would expect that a protein associated with SVs would promote its synaptic targeting. Several results suggest that the RAB-3 GTP-binding protein enhances UNC-57 recruitment to the SV pool. To test the role of RAB-3, we analyzed aex-3 mutants. The aex-3 gene encodes the GDP/GTP exchange factor for RAB-3 and AEX-6 Rab27 (AEX-3 Rab3GEF). Mutants lacking AEX-3 have an SV exocytosis defect that is very similar to the defect observed in rab-3; aex-6 Rab27 double mutants ( Mahoney et?al., 2006). As in other exocytosis mutants, photoactivated UNC-57 dispersed more slowly in aex-3 mutants (�� = 45.5 �� 5.1 s; p