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STIM 1 activation of adenylyl cyclase 6 connects Ca 2+ and cAMP signaling during melanogenesis
Author(s) -
Motiani Rajender K,
Tanwar Jyoti,
Raja Desingu Ayyappa,
Vashisht Ayushi,
Khanna Shivangi,
Sharma Sachin,
Srivastava Sonali,
Sivasubbu Sridhar,
Natarajan Vivek T,
Gokhale Rajesh S
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797597
Subject(s) - adenylyl cyclase , biology , signal transduction , microbiology and biotechnology , g protein , biochemistry
Endoplasmic reticulum ( ER )–plasma membrane ( PM ) junctions form functionally active microdomains that connect intracellular and extracellular environments. While the key role of these interfaces in maintenance of intracellular Ca 2+ levels has been uncovered in recent years, the functional significance of ER ‐ PM junctions in non‐excitable cells has remained unclear. Here, we show that the ER calcium sensor protein STIM 1 (stromal interaction molecule 1) interacts with the plasma membrane‐localized adenylyl cyclase 6 ( ADCY 6) to govern melanogenesis. The physiological stimulus α‐melanocyte‐stimulating hormone (α MSH ) depletes ER Ca 2+ stores, thus recruiting STIM 1 to ER ‐ PM junctions, which in turn activates ADCY 6. Using zebrafish as a model system, we further established STIM 1's significance in regulating pigmentation in vivo . STIM 1 domain deletion studies reveal the importance of Ser/Pro‐rich C‐terminal region in this interaction. This mechanism of cAMP generation creates a positive feedback loop, controlling the output of the classical α MSH ‐ cAMP ‐ MITF axis in melanocytes. Our study thus delineates a signaling module that couples two fundamental secondary messengers to drive pigmentation. Given the central role of calcium and cAMP signaling pathways, this module may be operative during various other physiological processes and pathological conditions.