ClInt1

ClInt1, short for Clathrin Interacting 1, is a conserved protein that participates in clathrin-mediated endocytosis. In vertebrates, the CLINT1 gene encodes a cytosolic protein that associates with the clathrin coat and with adaptor protein complex AP-2, helping to recruit cargo and stabilize forming vesicles. It localizes to sites of endocytosis at the plasma membrane and to the trans-Golgi network and early endosomes.

Discovery and nomenclature: The protein was identified as a clathrin-binding partner in proteomic and interaction screens, leading to its designation as CLINT1.

Structure and domains: ClInt1 contains coiled-coil regions that support dimerization and scaffolding, as well as motifs that mediate clathrin heavy chain binding. The protein lacks catalytic activity and is thought to function primarily via protein-protein interactions. The estimated mass is in the 60–70 kDa range.

Function and role: It acts as a scaffolding factor that links cargo to the clathrin coat during vesicle formation, interacting with AP-2, accessory proteins, and dynamin in some contexts. It is implicated in endocytic recycling and sorting between endosomes and the Golgi. Its activity is regulated by phosphorylation and cellular signaling pathways.

Expression and evolution: CLINT1 is evolutionarily conserved across vertebrates and is broadly expressed, with higher expression in brain and immune-related tissues in some species. Alternative splicing yields multiple isoforms with potentially distinct subcellular localizations.

Clinical relevance: No single disease association has been definitively established. Some studies report variants or altered expression in neurodevelopmental or psychiatric conditions, but evidence remains inconclusive.

See also: Clathrin-mediated endocytosis; AP-2 adaptor complex; clathrin heavy chain.