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The road to lysosome-related organelles: Insights from Hermansky-Pudlak syndrome and other rare diseases

Bowman, Shanna L., Bi‐Karchin, Jing, Le, Linh, Marks, Michael S.·2019·Traffic
DOI 10.1111/tra.12646PMC PMC6541516
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Abstract

Lysosome‐related organelles (LROs) comprise a diverse group of cell type‐specific, membrane‐bound subcellular organelles that derive at least in part from the endolysosomal system but that have unique contents, morphologies and functions to support specific physiological roles. They include: melanosomes that provide pigment to our eyes and skin; alpha and dense granules in platelets, and lytic granules in cytotoxic T cells and natural killer cells, which release effectors to regulate hemostasis and immunity; and distinct classes of lamellar bodies in lung epithelial cells and keratinocytes that support lung plasticity and skin lubrication. The formation, maturation and/or secretion of subsets of LROs are dysfunctional or entirely absent in a number of hereditary syndromic disorders, including in particular the Hermansky‐Pudlak syndromes. This review provides a comprehensive overview of LROs in humans and model organisms and presents our current understanding of how the products of genes that are defective in heritable diseases impact their formation, motility and ultimate secretion.

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  • The defects in rab32a, ap3m2, and hps5 mutants recapitulate phenotypes observed in canonical LRO systems, such as melanosome or dense granule disorders in HPS.

    “These defects recapitulate the phenotypes observed in canonical LRO systems, such as melanosome or dense granule disorders in HPS (22).”

    From Lysosome-related organelles orchestrate guanine crystal formation in pigment cells (2026) · cites this paper as [22]

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Metadata

Authors
Bowman, S. L., Bi‐Karchin, J., Le, L., & Marks, M. S.
Affiliations
Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia Research Institute Philadelphia Pennsylvania
ORCID
Marks, Michael S.
Venue
Traffic
Publisher
Wiley
Published
2019-05-29
Volume
20
Issue
6
Pages
404-435
ISSN
  • 1398-9219
  • 1600-0854
DOI
10.1111/tra.12646
PMC
PMC6541516
Cited by
219
References
8
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
  • National Institute of General Medical Sciences (K12 GM081259, R01 GM108807)
  • National Heart, Lung, and Blood Institute (T32 HL007439, R01 HL121323)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR048155)
  • National Eye Institute (R01 EY015625)
  • National Institutes of Health

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