Disease relevance of CLTCL1

• Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like) [1].
• Our Northern and Southern blot analyses of meningiomas clearly suggest the CLH-22 gene may be involved in the tumor development and can be considered as a candidate for a tumor suppressor [2].

High impact information on CLTCL1

• The trimeric CHC22 protein does not interact with clathrin heavy chain subunits nor bind significantly to clathrin light chains [3].
• CHC22 associates with the AP1 and AP3 adaptor complexes but not with AP2 [3].
• 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 [3].
• Together these results implicate CHC22 in TGN membrane traffic involving the cytoskeleton [3].
• CHC22 is implicated in specialized membrane organization in skeletal muscle [4].

Biological context of CLTCL1

• Analysis of sequence divergence patterns suggested that structural features of the CHCs were maintained after gene duplication, but new interactions with regulatory proteins evolved for the CHC22 isoform [4].
• Genes encoding CHC22 orthologues were found in several vertebrate species, with only a pseudogene present in mice [4].
• These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions [5].
• The chromosome 22 breakpoint disrupts the 3' coding region of the CLTCL gene and leads to a truncated transcript, strongly suggesting a role for this gene in the features found in this patient [6].
• We provide 5470 bp cDNA sequence covering the entire open reading frame of the CLH-22 gene [2].

Anatomical context of CLTCL1

• CHC22 expression is also increased in regenerating muscle fibers with the same time course as embryonic myosin, indicating a role in muscle repair [5].
• During myoblast differentiation, CHC22 expression is increased, initially localized with desmin and nestin and then preferentially segregated to the poles of fused myoblasts [5].
• The muscle isoform of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear to be distinct from those of well-characterized clathrin-coated vesicles [5].
• The CLTCL gene is constitutively expressed in lymphoid cells and therefore presumably contributes an active promoter for the CLTCL-ALK gene [1].

Other interactions of CLTCL1

• CHC17 is bound and regulated by LCa and LCb, whereas CHC22 does not functionally interact with either light chain [4].
• Clathrin isoform CHC22, a component of neuromuscular and myotendinous junctions, binds sorting nexin 5 and has increased expression during myogenesis and muscle regeneration [5].
• In mature muscle CHC22 is preferentially concentrated at neuromuscular and myotendinous junctions, suggesting a role at sarcolemmal contacts with extracellular matrix [5].

References