LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles.

ABSTRACT

LAMP2 (lysosomal associated membrane protein 2) is one of the major protein components of the lysosomal membrane. There currently exist three LAMP2 isoforms, LAMP2A, LAMP2B and LAMP2C, and they vary in distribution and function. LAMP2A serves as a receptor and channel for transporting cytosolic proteins in a process called chaperone-mediated autophagy (CMA). LAMP2B is required for autophagosome-lysosome fusion in cardiomyocytes and is one of the components of exosome membranes. LAMP2C is primarily implicated in a novel type of autophagy in which nucleic acids are taken up into lysosomes for degradation. In this review, the current evidence for the function of each LAMP2 isoform in various pathophysiological processes and human diseases, as well as their possible mechanisms, are comprehensively summarized. We discuss the evolutionary patterns of the three isoforms in vertebrates and provide technical guidance on investigating these isoforms. We are also concerned with the newly arising questions in this particular research area that remain unanswered. Advances in the functions of the three LAMP2 isoforms will uncover new links between lysosomal dysfunction, autophagy and human diseases.Abbreviation ACSL4 acyl-CoA synthetase long-chain family member 4; AD Alzheimer disease; Ag antigens; APP amyloid beta precursor protein; ATG14 autophagy related 14; AVSF autophagic vacuoles with unique sarcolemmal features; BBC3/PUMA BCL2 binding component 3; CCD C-terminal coiled coil domain; CMA chaperone-mediated autophagy; CVDs cardiovascular diseases; DDIT4/REDD1 DNA damage inducible transcript 4; ECs endothelial cells; ER endoplasmic reticulum; ESCs embryonic stem cells; GAPDH glyceraldehyde-3-phosphate dehydrogenase; GBA/ß-glucocerebrosidase glucosylceramidase beta; GSCs glioblastoma stem cells; HCC hepatocellular carcinoma; HD Huntington disease; HSCs hematopoietic stem cells; HSPA8/HSC70 heat shock protein family A (Hsp70) member 8; IL3 interleukin 3; IR ischemia-reperfusion; LAMP2 lysosomal associated membrane protein 2; LDs lipid droplets; LRRK2 leucine rich repeat kinase 2; MA macroautophagy; MHC major histocompatibility complex; MST1 macrophage stimulating 1; NAFLD nonalcoholic fatty liver disease; NFE2L2/NRF2 NFE2 like bZIP transcription factor 2; NLRP3 NLR family pyrin domain containing 3; PARK7 Parkinsonism associated deglycase; PD Parkinson disease; PEA15/PED proliferation and apoptosis adaptor protein 15; PKM/PKM2 pyruvate kinase M1/2; RA rheumatoid arthritis; RARA retinoic acid receptor alpha; RCAN1 regulator of calcineurin 1; RCC renal cell carcinoma; RDA RNautophagy and DNautophagy; RNAi RNA interference; RND3 Rho Family GTPase 3; SG-NOS3/eNOS deleterious glutathionylated NOS3; SLE systemic lupus erythematosus; TAMs tumor-associated macrophages; TME tumor microenvironment; UCHL1 ubiquitin C-terminal hydrolase L1; VAMP8 vesicle associated membrane protein 8.