Moesin and cortactin control actin-dependent multivesicular endosome biogenesis.
We used in vivo and in vitro strategies to study the mechanisms of multivesicular endosome biogenesis. We found that, whereas annexinA2 and ARP2/3 mediate F-actin nucleation and branching, respectively, the ERM protein moesin supports the formation of F-actin networks on early endosomes. We also found that moesin plays no role during endocytosis and recycling to the plasma membrane but is absolutely required, much like actin, for early-to-late-endosome transport and multivesicular endosome formation. Both actin network formation in vitro and early-to-late endosome transport in vivo also depend on the F-actin-binding protein cortactin. Our data thus show that moesin and cortactin are necessary for formation of F-actin networks that mediate endosome biogenesis or maturation and transport through the degradative pathway. We propose that the primary function of endosomal F-actin is to control the membrane remodeling that accompanies endosome biogenesis. We also speculate that this mechanism helps segregate tubular and multivesicular membranes along the recycling and degradation pathways, respectively.
Department of Biochemistry, University of Geneva, 1211 Geneva 4, Switzerland.
Olivia
O
Muriel
Department of Biochemistry, University of Geneva, 1211 Geneva 4, Switzerland.
Alejandra
A
Tomas
Department of Biochemistry, University of Geneva, 1211 Geneva 4, Switzerland.
Cameron C
CC
Scott
Department of Biochemistry, University of Geneva, 1211 Geneva 4, Switzerland jean.gruenberg@unige.ch.
Jean
J
Gruenberg
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D051356:Cortactin / Q000378:metabolism* / Q000502:physiology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D021381:Protein Transport
D000199:Actins; D002352:Carrier Proteins; D051356:Cortactin; C034037:F-actin-binding proteins; D008840:Microfilament Proteins; C071058:moesin