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ACTH/cAMP‐Stimulated Phosphorylation of Diaphanous 1 Regulates Mitochondrial Movement in H295R Human Adrenocortical Cells
Author(s) -
Li Donghui,
Sewer Marion B
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.732.5
Subject(s) - rhoa , phosphorylation , chemistry , medicine , microbiology and biotechnology , endocrinology , signal transduction , biology , biochemistry
Our lab has previously reported that adrenocorticotropin (ACTH) and dibutyryl cAMP (Bt 2 cAMP) stimulate mitochondrial movement, which regulates production of cortisol and adrenal androgens in human adrenocortical cells. We also found that phosphorylation of RhoA and its interaction with diaphanous 1 (DIAPH1) regulate mitochondrial movement. DIAPH1 is a RhoA effector that stimulates actin polymerization. Our mass spectrometry results indicated that DIAPH1 is a phosphoprotein that forms a complex with several proteins. Based on these results, we hypothesized that phosphorylation of DIAPH1 and its interaction with other proteins play a critical role in regulating mitochondrial movement. To test this hypothesis, we generated a phospho‐specific DIAPH1 antibody against T751 (Threonine) to probe the phosphorylation of DIAPH1. We found that ACTH/cAMP regulates the phosphorylation of DIAPH1 through MEK/ERK signaling pathway. This study further identified that phosphorylated DIAPH1 at T751 is key for controlling ACTH/cAMP‐stimulated mitochondrial movement and the interaction of DIAPH1 with its binding proteins. Taken together, our findings establish phosphorylation of DIAPH1 in regulating mitochondrial trafficking. This study is supported by NSF MCB1005815.