Lysosomal enzyme trafficking factor

Definition:

Required for mannose-6-phosphate-dependent trafficking of lysosomal enzymes. LYSET bridges GlcNAc-1-phosphate transferase (GNPTAB), to the membrane-bound transcription factor site-1 protease (MBTPS1), thus allowing proteolytic activation of the GNPTAB. GNPTAB is involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. LYSET is thus an essential factor for maturation and delivery of lysosomal hydrolases.; (Microbial infection) Essential for infection by muliple viruses, including SARS-CoV-2, that utilize activated cathepsins for entry after M6P-dependent lysosomal transport.

References:

[1]. Weichao Zhang, et al. GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway. Nat Commun. 2022 Sep 12;13(1):5351. [Content Brief]

[2]. Catarina Pechincha, et al. Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular proteins. Science. 2022 Oct 7;378(6615):eabn5637. [Content Brief]

[3]. Christopher M Richards, et al. The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection. Science. 2022 Oct 7;378(6615):eabn5648. [Content Brief]

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