Zhou, D;
Eraslan, Z;
Miller, D;
Taylor, I;
You, J;
Grondin, SJ;
Vega, M;
Manga, P;
Goff, PS;
Sviderskaya, EV;
et al.
Zhou, D; Eraslan, Z; Miller, D; Taylor, I; You, J; Grondin, SJ; Vega, M; Manga, P; Goff, PS; Sviderskaya, EV; Gross, SS; Chen, Q; Zippin, JH
(2024)
Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.
Pigment Cell Melanoma Res.
ISSN 1755-148X
https://doi.org/10.1111/pcmr.13177
SGUL Authors: Sviderskaya, Elena Vladimirovna
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Abstract
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.
Item Type: |
Article
|
Additional Information: |
Accepted manuscript file contains the information that is in a separate file Appendix S1 on the publisher website.
This is the peer reviewed version of the following article: Zhou, D., Eraslan, Z., Miller, D., Taylor, I., You, J., Grondin, S. J., Vega, M., Manga, P., Goff, P. S., Sviderskaya, E. V., Gross, S. S., Chen, Q., & Zippin, J. H. (2024). Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis. Pigment Cell & Melanoma Research, 00, 1–11. https://doi.org/10.1111/pcmr.13177, which has been published in final form at https://doi.org/10.1111/pcmr.13177. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. |
Keywords: |
NAADP, adenylyl cyclases, melanocytes, melanosomes, oculocutaneous albinism, adenylyl cyclases, melanocytes, melanosomes, NAADP, oculocutaneous albinism, adenylyl cyclases, melanocytes, melanosomes, NAADP, oculocutaneous albinism, 06 Biological Sciences, 11 Medical and Health Sciences, Dermatology & Venereal Diseases |
SGUL Research Institute / Research Centre: |
Academic Structure > REF 2021 user group |
Journal or Publication Title: |
Pigment Cell Melanoma Res |
ISSN: |
1755-148X |
Language: |
eng |
Dates: |
Date | Event |
---|
6 June 2024 | Published Online | 24 May 2024 | Accepted |
|
Publisher License: |
Publisher's own licence |
Projects: |
Project ID | Funder | Funder ID |
---|
UNSPECIFIED | Dermatology Foundation | UNSPECIFIED | UNSPECIFIED | NIEHS NIH HHS | UNSPECIFIED | UNSPECIFIED | NINDS NIH HHS | UNSPECIFIED | UNSPECIFIED | Pfizer | UNSPECIFIED | UNSPECIFIED | NIAMS NIH HHS | UNSPECIFIED | R21 CA224391 | NCI NIH HHS | UNSPECIFIED | UNSPECIFIED | National Organization for Albinism and Hypopigmentation | UNSPECIFIED |
|
PubMed ID: |
38844435 |
Web of Science ID: |
WOS:001245009700001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/116724 |
Publisher's version: |
https://doi.org/10.1111/pcmr.13177 |
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