Auxilin (DNAJC6) Summary

Auxilin (DNAJC6) is a co-chaperone protein that recruits the heat shock protein HSPA8/HSC70 to clathrin-coated vesicles (CCVs) and facilitates ATP-dependent clathrin uncoating (UniProt: O75061). It plays essential roles in clathrin-mediated endocytosis, synaptic vesicle recycling, and intracellular trafficking by promoting the stepwise dissociation of clathrin cages into component triskelia.

Mutations in DNAJC6 are associated with Parkinson disease (PARK19A and PARK19B; UniProt: O75061), juvenile-onset and early-onset forms characterized by dopaminergic neuronal loss in the substantia nigra and Lewy body pathology. The protein's function in vesicular trafficking and synaptic homeostasis implicates it in neuronal integrity and dopamine neurotransmission.

Auxilin shows reduced abundance in Alzheimer's disease brain compared to age-matched controls (Chaparral AD proteomics; mean log2FC = −0.98, direction: down). This downregulation may impair clathrin-mediated endocytosis and neuronal vesicle dynamics, potentially contributing to amyloid-β or tau pathology progression through defective synaptic protein recycling mechanisms characteristic of AD neurodegeneration.