Myo1c regulates lipid raft recycling to control cell spreading, migration and Salmonella invasion.
A balance between endocytosis and membrane recycling regulates the composition and dynamics of the plasma membrane. Internalization and recycling of cholesterol- and sphingolipid-enriched lipid rafts is an actin-dependent process that is mediated by a specialized Arf6-dependent recycling pathway. Here, we identify myosin1c (Myo1c) as the first motor protein that drives the formation of recycling tubules emanating from the perinuclear recycling compartment. We demonstrate that the single-headed Myo1c is a lipid-raft-associated motor protein that is specifically involved in recycling of lipid-raft-associated glycosylphosphatidylinositol (GPI)-linked cargo proteins and their delivery to the cell surface. Whereas Myo1c overexpression increases the levels of these raft proteins at the cell surface, in cells depleted of Myo1c function through RNA interference or overexpression of a dominant-negative mutant, these tubular transport carriers of the recycling pathway are lost and GPI-linked raft markers are trapped in the perinuclear recycling compartment. Intriguingly, Myo1c only selectively promotes delivery of lipid raft membranes back to the cell surface and is not required for recycling of cargo, such as the transferrin receptor, which is mediated by parallel pathways. The profound defect in lipid raft trafficking in Myo1c-knockdown cells has a dramatic impact on cell spreading, cell migration and cholesterol-dependent Salmonella invasion; processes that require lipid raft transport to the cell surface to deliver signaling components and the extra membrane essential for cell surface expansion and remodeling. Thus, Myo1c plays a crucial role in the recycling of lipid raft membrane and proteins that regulate plasma membrane plasticity, cell motility and pathogen entry.
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
Hemma
H
Brandstaetter
John
J
Kendrick-Jones
Folma
F
Buss
D001692:Biological Transport; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism; D005089:Exocytosis; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D024461:Myosin Type I / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology*; D012486:Salmonella typhimurium / Q000502:physiology*
D008563:Membrane Lipids; D002784:Cholesterol; D024461:Myosin Type I; C460367:MYO1C protein, human