In addition, Rab8 and molecule interacting with CasL 3 (MICA元) cooperate in controlling the docking and fusion of exocytotic carriers ( Grigoriev et al., 2011). It is also required for the outgrowth of the primary cilium, and regulates apical protein localization in intestinal cells ( Nachury et al., 2007 Sato et al., 2007 Yamamura et al., 2008). Rab8 plays a role in the exocytosis of AP-1B-dependent cargo ( Ang et al., 2003). Small GTPase Rab proteins and their effectors regulate membrane trafficking between different intracellular compartments ( Stenmark, 2009 Wandinger-Ness and Zerial, 2014). Secreted cargoes are transported from the endoplasmic reticulum to the Golgi apparatus (GA) and are then addressed to the plasma membrane.
Membrane trafficking is a tightly regulated process required for plasma membrane (PM) homeostasis, adhesion, and cell polarity. Our results reveal a new role for MICAL-L1 in cargo delivery to the plasma membrane. Interestingly, two hydrophobic residues at the C-terminus of MICAL-L1 appeared to be important for phosphatidic acid binding, and for association with membrane tubules. The process of membrane tubulation was monitored in vitro, and we observe that recombinant MICAL-L1-RBD domain may contribute to promote PACSINs-mediated membrane tubulation. Using a synchronized secretion assay, we report that the shRNA-mediated depletion of MICAL-L1 impaired the delivery of a subset of cargo proteins to the cell surface. Super resolution STORM microscopy suggested at the molecular level, a very close association of MICAL-L1 and microdomains in the Golgi cisternae. Using confocal microscopy, we showed that MICAL-L1 was associated with tubulo-vesicular structures and exhibited a significant colocalization with markers of the Golgi apparatus and recycling endosomes.
Small GTPase Rab and their effectors play a key role in membrane trafficking. Secreted proteins are transported along intracellular route from the endoplasmic reticulum through the Golgi before reaching the plasma membrane.
0 kommentar(er)
