title: Hook1, microtubules, and Rab22: mediators of selective sorting of clathrin-independent endocytic cargo proteins on endosomes.
abstract: Clathrin-independent endocytosis (CIE) mediates the internalization of many plasma membrane (PM) proteins involved in homeostasis, immune response, and signaling. CIE cargo molecules are internalized independent of clathrin, and dynamin, and modulated by the small G protein Arf6. After internalization the CIE cargo proteins either follow a default pathway of trafficking to lysosomes for degradation or follow a pathway where they are routed directly to the recycling endosomes for return to the PM. The selective endosomal sorting of molecules like CD44, CD98, and CD147, which are involved in cell-cell and cell-extracellular interactions, indicates that sorting mechanisms dictate the post-endocytic fate of CIE cargo proteins. In a recent study, we identified sorting signals that specify the endosomal trafficking of CIE cargo proteins and uncover a role for Hook1 as an endosomal cargo adaptor that routes CIE cargo to the recycling endosomes. Furthermore, we found that Hook1, microtubules, and Rab22a work in coordination to directly recycle the cargo and facilitate cell spreading. Here, we discuss our current view on the endosomal sorting of CIE cargo proteins and their molecular regulators.
authors.affiliation: Cell Biology and Physiology Center; National Heart, Lung, and Blood Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Lymarie
authors.initials: L
authors.lastname: Maldonado-Báez
authors.affiliation: Cell Biology and Physiology Center; National Heart, Lung, and Blood Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Donaldson
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D051926:Basigin / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000089982:ADP-Ribosylation Factor 6; D002966:Clathrin; D027261:Fusion Regulatory Protein-1; D018960:Hyaluronan Receptors; D008869:Microtubule-Associated Proteins; D021382:Protein Sorting Signals; C484191:RAB22A protein, human; C471055:hook1 protein, human; D051926:Basigin; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; D020691:rab GTP-Binding Proteins
keywords: CD147; Hook1; Rab22; Rab22a; basigin; clathrin-independent endocytosis; endosomal sorting; microtubules; recycling; sorting signals