A novel clathrin homolog that co-distributes with cytoskeletal components functions in the trans-Golgi network

Abstract

A clathrin homolog encoded on human chromosome 22 (CHC22) displays distinct biochemistry, distribution and function compared with conventional clathrin heavy chain (CHC17), encoded on chromosome 17. CHC22 protein is upregulated during myoblast differentiation into myotubes and is expressed at high levels in muscle and at low levels in non-muscle cells, relative to CHC17. The trimeric CHC22 protein does not interact with clathrin heavy chain subunits nor bind significantly to clathrin light chains. CHC22 associates with the AP1 and AP3 adaptor complexes but not with AP2. In non-muscle cells, CHC22 localizes to perinuclear vesicular structures, the majority of which are not clathrin coated. Treatments that disrupt the actin-myosin cytoskeleton or affect sorting in the trans-Golgi network (TGN) cause CHC22 redistribution. Overexpression of a subdomain of CHC22 induces altered distribution of TGN markers. Together these results implicate CHC22 in TGN membrane traffic involving the cytoskeleton.

Interaction between autophagic vesicles and the Coxiella-containing vacuole requires CLTC (clathrin heavy chain)

“…Hence, this data suggests the possibility of a new, additional function of CLTC in the context of autophagy. Recent studies have demonstrated that CLTC exists in 2 isoforms, CHC17 and CHC22, and that these isoforms have different functions [30,31]. CHC17 binds to clathrin light chains (CLC) and AP2 at the plasma membrane for endocytosis, however CHC22 binds neither CLC or AP2 and has been described to aid in trafficking of SLC2A4/GLUT4 (solute carrier family 2 member 4) [32].…”

The δ subunit of AP-3 is required for efficient transport of VSV-G from the trans-Golgi network to the cell surface

“…Given the ability of VSV-G to usurp the function of the putative AP-3-regulated pathway, we suggest that it is both the type of cargo and the type of coat that dictates the targeting information recruited to or retained in carrier intermediates exiting the TGN. Indeed, two distinct classes of AP-3-coated structures, clathrin-associated and clathrin-independent AP-3s, have been reported (61), and a third may involve a novel form of clathrin (62). Thus, a combination of cargo, AP-3, and other coat components may favor coassembly with specific vesicle targeting proteins that direct the fate of the transport container to either the lysosome (yeast vacuole) (i.e., LAMP1), regulated secretory lysosome (i.e., tyrosinase), or constitutive pathways (VSV-G, other?).…”

Sequencing study on familial lung squamous cancer

“…In the study by DeWan et al, it was found that one mutation, I303L, in PDE4DIP may be the causative variant in hereditary asthma (23). CLTCL1 is a member of the clathrin family, which plays essential roles in intracellular traffic and centrosomal stabilization (24). Mutations or the abnormal expression of CLTCL1 have been reported to be associated with breast cancer, meningioma and pulmonary valve stenosis (25).…”