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. 2013 Sep-Dec;3(5):141-6.
doi: 10.4161/bioa.26638. Epub 2013 Sep 1.

Hook1, microtubules, and Rab22: mediators of selective sorting of clathrin-independent endocytic cargo proteins on endosomes

Lymarie Maldonado-Báez  1 , Julie G Donaldson  1
Affiliations

Hook1, microtubules, and Rab22: mediators of selective sorting of clathrin-independent endocytic cargo proteins on endosomes

Lymarie Maldonado-Báez et al. Bioarchitecture. 2013 Sep-Dec.

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.

Keywords: CD147; Hook1; Rab22; Rab22a; basigin; clathrin-independent endocytosis; endosomal sorting; microtubules; recycling; sorting signals.

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Figures

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Figure 1. General model for the endosomal sorting of CIE cargo proteins. CIE cargo proteins are internalized by a pathway independent of clathrin, dynamin and associated with the small G protein Arf6. Prototypical CIE cargo proteins (red bars) enter the cell in Arf6-positive endocytic vesicles that either fuse with or mature into Rab5-, EEA1- and transferrin- positive endosomes. Then, the cargo proteins are either targeted to late endosomes (LE) for degradation or recycled back to the PM in a Rab22/Rab11 dependent manner. CIE cargo proteins harboring cytoplasmic sorting motifs (green bars) avoid trafficking to EEA1- and transferrin- (TfR/Tf; black bars) associated endosomes and traffic directly to the recycling endosomes (RE). Hook1 facilitates the directed recycling of CIE cargo proteins, such as CD98 and CD147, through its interaction with microtubules and their cytoplasmic sequences on sorting endosomes.
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Figure 2. Hook1 and Rab22a colocalize with CIE cargo on recycling tubular endosomes. HeLa cells expressing endogenous levels of Hook1 and overexpressing the constitutively active Rab22a mutant (GFP-Rab22a Q64L) were incubated with anti-CD147 antibody for 30 min at 37°C to allow internalization of bound antibodies. Hook1, Rab22a and CD147 meet on puncta and tubular endosomal structures after internalization.
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