Abstract
During the vesicular trafficking process, cellular membranes undergo dynamic morphological changes, in particular at the vesicle generation and fusion steps. Changes in membrane shape are regulated by small GTPases, coat proteins and other accessory proteins, such as BAR domain-containing proteins. In addition, membrane deformation entails changes in the lipid composition as well as asymmetric distribution of lipids over the two leaflets of the membrane bilayer. Given that P4-ATPases, which catalyze unidirectional flipping of lipid molecules from the exoplasmic to the cytoplasmic leaflets of the bilayer, are crucial for the trafficking of proteins in the secretory and endocytic pathways, changes in the lipid composition are involved in the vesicular trafficking process. Membrane remodeling is under complex regulation that involves the composition and distribution of lipids as well as assembly of proteins.
Highlights
Biological membranes separate the interior of the cell from the external environment, and bring about compartmentalization of distinct subcellular organelles
There has been no direct evidence indicating that mammalian P4-ATPases play essential roles in membrane trafficking, earlier studies showed that changes in lipid composition are involved in vesicular trafficking in a human erythroleukemia cell line, K562 [32]: endocytosis is stimulated by extracellular application of PS or PE, but partially inhibited by the addition of lyso-PS, which cannot translocate across the plasma membrane [32]
Arl1 expression, indicating that Arl1 is required for targeting arfaptin to Golgi membranes. It is not clear whether association of Arl1 or lipid modification provides the initial cue for membrane deformation, it is clear that arfaptin molecules recruited onto Golgi membranes through interaction with Arl1 sense and stabilize membrane curvature, and thereby facilitate tubule formation, probably through oligomerization like other BAR domain proteins [77,78,79,80] (Figure 1D)
Summary
Biological membranes separate the interior of the cell from the external environment, and bring about compartmentalization of distinct subcellular organelles. Dynamic membrane shape changes occur during formation of the vesicles and tubules that mediate cargo delivery in the secretory and endocytic pathways. These carrier intermediates vary in shape, from small vesicles (~50 nm) and thin tubules to tubular-saccular carriers [1,2,3]. Formation of carrier intermediates is driven through a complex process that involves modification and changes in composition and distribution of lipids, as well as local assembly of coat protein complexes and proteins involved in sensing and forming membrane curvature. Insertion of amphipathic helices into the membrane subdomain is required for curvature generation; proteins containing BAR (Bin/Amphiphysin/Rvs) domains, which form a crescent-like homodimer, are required for sensing and stabilizing this curvature. We consider the interplays among these proteins that generate and stabilize membrane curvature in the context of membrane trafficking
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
