Lamp1 (mouse, UniProt P11438) - manual literature synthesis

No deep-research provider was available for this session. This file is a manual
synthesis from the cached publications in publications/ and the UniProt record
(Lamp1-uniprot.txt). Each claim carries its provenance.

Identity and structure

• Lamp1 encodes lysosome-associated membrane glycoprotein 1 (LAMP-1, CD107a, LGP-120),
  a single-pass type I membrane protein with a large, heavily N- and O-glycosylated
  luminal region made of two beta-prism subdomains separated by a proline-rich hinge,
  a single transmembrane helix and a short cytoplasmic tail carrying a
  lysosome-targeting tyrosine motif [file:mouse/Lamp1/Lamp1-uniprot.txt "TOPO_DOM 25..370 /note=\"Lumenal\""];
  PMID:27663661.
• LAMP-1 and LAMP-2 are "the most abundant protein components in lysosome membranes"
  PMID:27663661. Belongs to the LAMP family (PANTHER PTHR11506:SF27; Pfam PF01299).

Localization

• Lysosomal and late endosomal limiting membrane; shuttles via the plasma membrane
  [file:mouse/Lamp1/Lamp1-uniprot.txt "This protein shuttles between lysosomes, endosomes, and the plasma membrane"].
• Used universally as a lysosome marker in mouse cells; dozens of MGI IDA annotations
  derive from marker use (e.g. PMID:24841562;
  PMID:26284655).
• Also on lysosome-related organelles: cytolytic granules of NK/CTL (appearing on the cell
  surface after degranulation) PMID:23847195,
  melanosomes PMID:11266470,
  phagolysosomes PMID:23395172,
  autolysosomes PMID:26284655.

Molecular function

• Direct inhibition of the lysosomal cation/proton channel TMEM175 (shown for human
  LAMP-1/LAMP-2): PMID:37390818;
  PMID:37390818.
  The mouse protein carries this by similarity (UniProt FUNCTION, ECO:0000250 from P11279).
• Binds the TMD0 domain of the lysosomal peptide transporter TAPL/ABCB9 and stabilizes it
  against lysosomal degradation PMID:22641697;
  PMID:22641697.

Mouse genetics

• Lamp1-/- mice are viable and fertile with essentially normal lysosomes; LAMP-2 is
  upregulated PMID:10212251;
  PMID:10212251.
• Lamp1/Lamp2 double knockouts die at E14.5-16.5 with autophagic vacuole accumulation
  and cholesterol storage PMID:15121881.
  Cholesterol storage is rescued by LAMP-2a but not LAMP-1 PMID:15121881.

Cytotoxic lymphocytes

• Surface CD107a protects NK cells from their own granule contents; Lamp1-/- mouse NK
  cells show increased degranulation-associated apoptosis
  PMID:23847195.
• In human NK cells, LAMP1 is needed for perforin delivery to lytic granules and granule
  movement PMID:23632890.

Caveat on PMID:22147702

PMID:22147702 (alpha-TTP and chloroquine toxicity) uses an anti-rat LAMP-1 antibody as a
lysosomal marker in rat McARH7777 hepatoma cells PMID:22147702.
It contains no experiment on mouse Lamp1 function; it is background support for LAMP-1
as a lysosomal membrane marker only.