Lysosomal-associated transmembrane protein 4B

Definition:

Required for optimal lysosomal function. Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation. Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation. Plays a role as negative regulator of TGFB1 production in regulatory T cells. Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways.

References:

[1]. Tomas Blom, et al. LAPTM4B facilitates late endosomal ceramide export to control cell death pathways. Nat Chem Biol. 2015 Oct;11(10):799-806. [Content Brief]

[2]. Ruth Milkereit, et al. LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation. Nat Commun. 2015 May 22;6:7250. [Content Brief]

[3]. Xiaojun Tan, et al. LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation. EMBO J. 2015 Feb 12;34(4):475-90. [Content Brief]

[4]. Silvia Vergarajauregui, et al. LAPTMs regulate lysosomal function and interact with mucolipin 1: new clues for understanding mucolipidosis type IV. J Cell Sci. 2011 Feb 1;124(Pt 3):459-68. [Content Brief]

[5]. Caroline Huygens, et al. Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells. J Biol Chem. 2015 Aug 14;290(33):20105-16. [Content Brief]

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