Evidence map›Paper›PMID 38844435›Full record

ArticlePigment cell & melanoma research2024

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

Dalee Zhou, Zuhal Eraslan, Dawson Miller, Isobel Taylor, Jaewon You, Samuel J Grondin, Martha Vega, Prashiela Manga, Philip S Goff, Elena V Sviderskaya and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pigment cell & melanoma research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Dalee ZhouDepartment of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Zuhal EraslanDepartment of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Dawson MillerDepartment of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Isobel TaylorDepartment of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Jaewon YouDepartment of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Samuel J GrondinDepartment of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Martha VegaThe Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.
Prashiela MangaThe Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.
Philip S GoffCell Biology Research Section, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.ORCID 0000-0003-4371-5527
Elena V SviderskayaCell Biology Research Section, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
Steven S GrossDepartment of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Qiuying ChenDepartment of Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Jonathan H ZippinDepartment of Dermatology, Weill Cornell Medical College of Cornell University, New York, New York, USA.ORCID 0000-0002-5882-0189

Funding

CANCER PHARMACOLOGYT32CA062948 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LORRAINE J GUDAS · 1994 to 2026
$12.1M
Mechanisms of cAMP-dependent regulation of melanosome pHR01AR077664 · NIAMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Jonathan Hale Zippin · 2021 to 2026
$3.6M
Metabolic remodeling of skeletal muscle in mitochondrial myopathiesR01AR076029 · NIAMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, QIUYING, D'AURELIO, MARILENA · 2020 to 2024
$2.7M
Pho-m6A assay: A phosphoselective method to quantify dynamics of m6A in mRNAR21ES032347 · NIEHS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, QIUYING, JAFFREY, SAMIE R · 2020 to 2021
$466k
Modulation of intermediate metabolism, a new therapeutic approach for mitochondrial encephalomyopathiesR21NS118233 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, QIUYING, D'AURELIO, MARILENA · 2021 to 2021
$466k
Uncovering the role of m6A in the melanocyte response to ultraviolet lightR21CA224391 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI JAFFREY, SAMIE R, ZIPPIN, JONATHAN HALE · 2018 to 2019
$399k
Dermatology FoundationNational Organization for Albinism and HypopigmentationNCI NIH HHS R21 CA224391NCI NIH HHS T32 CA062948NIAMS NIH HHS R01 AR076029NIAMS NIH HHS R01 AR077664NIEHS NIH HHS R21 ES032347NINDS NIH HHS R21 NS118233Pfizer
6 · The paper itself

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.

Indexed as

Adenylyl CyclasesMelaninsMelanosomesAnimalsCalcium ChannelsHumansHydrogen-Ion ConcentrationMelanocytesMiceSignal TransductionSolubilityTwo-Pore ChannelsAdenylyl CyclasesCalcium ChannelsMelaninsTPCN2 protein, humanTwo-Pore Channelsadenylyl cyclasesmelanocytesmelanosomesNAADPoculocutaneous albinism

Identifiers

PMID38844435
PMCPMC11479823

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.