From: Chaperone-mediated autophagy: roles in neurodegeneration
CMA substrate/binding Protein | Physiology function | Pathogenic mutant variants | Molecular mechanism | Effects on CMA activity | Disease |
---|---|---|---|---|---|
Neuronal deubiquitinating enzyme | I93M | Abnormal binding to LAMP2A to block degradation by CMA substrates | ↓ | PD | |
Function is not well understood | A30P, A53T | Abnormally high affinity binding to LAMP2A to prevent the translocation across the lysosomal membrane | ↓ | PD | |
Involved in mitogen-activated protein kinase, protein translation control, programmed cell death, and activity in cytoskeleton dynamics | G2019S | Interference with the organization of the CMA translocation complex and cause defective CMA | ↓ | PD | |
Stabilization of microtubules | FTDP-17 mutation (TauRDΔK280) | Oligomerization at the surface of lysosomes to disrupt the membrane integrity and blockage of normal CMA function | ↓ | AD | |
Regulator of calcineurin 1 (RCAN1) [61] | A mediator of stress- and Aβ-induced neuronal death | \ | Mechanistic effects on lysosome unclear | ↓ | AD |
Unclear and essential for development | Expansion of polyglutamine | Increased clearance via regulation of LAMP2A and lys-Hsc70 | ↑(early stages); ↓(late stages) | HD |