Sec15B Inhibitors

Chemical inhibitors of Sec15B disrupt various stages of vesicular trafficking and cytoskeletal dynamics, thereby impeding the protein's role in vesicle docking and fusion at the plasma membrane. Brefeldin A hampers vesicular transport by inhibiting the ARF1/COPI interaction, which is a process fundamental to the movement of vesicles from the ER to the Golgi apparatus. Similarly, Exo1 and Golgicide A target GBF1, a guanine nucleotide exchange factor (GEF) for ARF1, necessary for the vesicle formation from the ER. This inhibition leads to a reduction in vesicle trafficking, indirectly curtailing Sec15B's function in exocytosis. Dynasore and MiTMAB both target dynamin GTPase activity, which is critical for the release of clathrin-coated vesicles. By preventing vesicle scission, these inhibitors ultimately decrease the number of vesicles available for Sec15B to act upon, thereby reducing its function in vesicle targeting and fusion.

Further disruption of Sec15B's function is achieved by compounds such as Nocodazole and Cytochalasin D, which disintegrate microtubules and actin filaments, respectively. Such disintegration is detrimental to the delivery and movement of vesicles within the cell, crucial stages where Sec15B exerts its effect. Latrunculin B and Jasplakinolide affect actin dynamics differently; Latrunculin B binds to actin monomers and prevents their polymerization, whereas Jasplakinolide stabilizes the filaments, preventing their proper dynamics. Both actions result in impaired vesicle docking and fusion processes involving Sec15B. The inhibition of Cdc42 by ML141 also disrupts actin filament organization, affecting vesicle movement towards the plasma membrane. SecinH3 targets cytohesins, leading to compromised ARF GTPase activity which is essential in mediating vesicular transport and, by extension, Sec15B's role. Lastly, SMIFH2 inhibits formin-mediated actin nucleation, further disrupting the actin filament formation that is necessary for the proper localization and function of Sec15B in the cell.