Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.

NAADP adenylyl cyclases melanocytes melanosomes oculocutaneous albinism

Journal

Pigment cell & melanoma research
ISSN: 1755-148X
Titre abrégé: Pigment Cell Melanoma Res
Pays: England
ID NLM: 101318927

Informations de publication

Date de publication:
06 Jun 2024
Historique:
revised: 25 04 2024
received: 09 08 2023
accepted: 24 05 2024
medline: 7 6 2024
pubmed: 7 6 2024
entrez: 6 6 2024
Statut: aheadofprint

Résumé

Melanosomal pH is important for the synthesis of melanin as the rate-limiting enzyme, tyrosinase, is very pH-sensitive. The soluble adenylyl cyclase (sAC) signaling pathway was recently identified as a regulator of melanosomal pH in melanocytes; however, the melanosomal proteins critical for sAC-dependent regulation of melanosomal pH were undefined. We now systematically examine four well-characterized melanosomal membrane proteins to determine whether any of them are required for sAC-dependent regulation of melanosomal pH. We find that OA1, OCA2, and SLC45A2 are dispensable for sAC-dependent regulation of melanosomal pH. In contrast, TPC2 activity is required for sAC-dependent regulation of melanosomal pH and melanin synthesis. In addition, activation of TPC2 by NAADP-AM rescues melanosomal pH alkalinization and reduces melanin synthesis following pharmacologic or genetic inhibition of sAC signaling. These studies establish TPC2 as a critical melanosomal protein for sAC-dependent regulation of melanosomal pH and pigmentation.

Identifiants

pubmed: 38844435
doi: 10.1111/pcmr.13177
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Dermatology Foundation
Organisme : Pfizer
Organisme : NCI NIH HHS
Pays : United States
Organisme : NIAMS NIH HHS
Pays : United States
Organisme : National Organization for Albinism and Hypopigmentation
Organisme : NIEHS NIH HHS
Pays : United States
Organisme : NINDS NIH HHS
Pays : United States

Informations de copyright

© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Auteurs

Dalee Zhou (D)

Department of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Zuhal Eraslan (Z)

Department of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Dawson Miller (D)

Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Isobel Taylor (I)

Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Jaewon You (J)

Department of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Samuel J Grondin (SJ)

Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Martha Vega (M)

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.

Prashiela Manga (P)

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.

Philip S Goff (PS)

Cell Biology Research Section, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.

Elena V Sviderskaya (EV)

Cell Biology Research Section, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.

Steven S Gross (SS)

Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Qiuying Chen (Q)

Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Jonathan H Zippin (JH)

Department of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.

Classifications MeSH