PICALM


Description

The PICALM (phosphatidylinositol binding clathrin assembly protein) is a protein-coding gene located on chromosome 11.

PICALM, also known as Phosphatidylinositol binding clathrin assembly protein, is a protein encoded by the PICALM gene in humans. It interacts with CLTC. Certain alleles of this gene have been linked to an increased risk of developing late-onset Alzheimer's disease.

PICALM is a cytoplasmic adapter protein that plays a key role in clathrin-mediated endocytosis, a process essential for internalizing cell receptors, synaptic transmission, and removing apoptotic cells. It recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of the plasma membrane, leading to the formation of clathrin-coated vesicles (CCVs). PICALM also regulates the size and maturation of CCVs by directly sensing and driving membrane curvature. Besides binding to clathrin, PICALM mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors), including VAMP2, VAMP3, VAMP4, VAMP7, and VAMP8, between plasma membranes and endosomes. This PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors, ultimately modulating autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF).

PICALM is also known as CALM, CLTH, LAP.

Associated Diseases


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