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Cited by 174Autophagy in Disease and TherapyCellular transport and secretionCalcium signaling and nucleotide metabolism

LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles

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Qiao, Lei, Hu, Jiayi, Qiu, Xiaohan, Wang, Chunlin, Peng, Jieqiong, Zhang, Cheng, Zhang, Meng, Lu, Huixia +1 more·2023·Autophagy
DOI 10.1080/15548627.2023.2235196PMC PMC10549195
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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/β-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

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  • CMA is a selective autophagy mechanism disrupted early in Alzheimer's disease, partly due to reduced LAMP2A expression.

    “CMA is increasingly recognized as a selective mechanism disrupted early in AD, partly due to reduced LAMP2A expression [140, 141].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [140]

    Table 2 (Limitations; page unavailable) says CMA is inhibited in early AD stages, and the LAMP2A section describes CMA as selective. The paper does not say that reduced LAMP2A expression partly causes this early disruption in AD; its reported reductions concern aging and Parkinson disease, while the AD mouse result concerns an experimental LAMP2A knockout. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Defective CMA reduces degradation of tau and α-synuclein, increasing aggregation-prone species.

    “Third, defective CMA reduces the degradation of tau and α-synuclein, increasing aggregation-prone species [140, 141].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [140]

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Cited by

Sorted by citations

Authors
Qiao, L., Hu, J., Qiu, X., Wang, C., Peng, J., Zhang, C., Zhang, M., Lu, H., & Chen, W.
Affiliations
  • Shandong University (CN)
  • Shandong Tumor Hospital (CN)
Corresponding author
  • Zhang, Meng
  • Lu, Huixia
  • Chen, Wenqiang
ORCID
Venue
Autophagy
Publisher
Informa UK Limited
Published
2023-07-21
Volume
19
Issue
11
Pages
2837-2852
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
DOI
10.1080/15548627.2023.2235196
PMC
PMC10549195
OpenAlex
W4384818697
Cited by
174
References
8
Citations by year
2026: 58 · 2025: 76 · 2024: 38 · 2023: 2
FWCI
6.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Autophagy (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2021YFF0501404 and No. 2021YFF0501403)
  • the National Natural Science Foundation of China (82200303 and No. 81770436)
  • the Postdoctoral Science Foundation of China (2022T150387)
  • the Shandong Provincial Natural Science Foundation (ZR2022QH056)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
LAMP2A, Lamp2b, lysosomal membrane, chaperone-mediated autophagy, autophagosome-lysosome fusion, exosomes, lysosomal dysfunction, lysosomal storage disease, neurodegenerative diseases
MeSH terms
Animals, Autophagy, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Lysosomes, Amyloid beta-Peptides, Protein Isoforms, Endothelial Cells, Apoptosis Regulatory Proteins, Lysosomal-Associated Membrane Protein 2, Tumor Microenvironment

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