The lysosomal trafficking regulator "LYST": an 80-year traffic jam

Front Immunol. 2024 May 7:15:1404846. doi: 10.3389/fimmu.2024.1404846. eCollection 2024.

Abstract

Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications.

Keywords: Chédiak-Higashi syndrome; LYST; beige; cancer; immunotherapy; lysosomes; vesicle traffic; wound healing.

Publication types

  • Review

MeSH terms

  • Animals
  • Chediak-Higashi Syndrome / genetics
  • Humans
  • Lysosomes* / metabolism
  • Mutation
  • Protein Transport
  • Vesicular Transport Proteins* / genetics
  • Vesicular Transport Proteins* / metabolism

Substances

  • LYST protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health through 1R01HL157491-01 awarded to ChB, F31HL1145962 supporting CaB, and 3R01HL157491-02S1 supporting MT.