Interplay between myotubularins and Ca2+ homeostasis.

The myotubularin family, encompassing myotubularin 1 (MTM1) and 14 myotubularin-related proteins (MTMRs), represents a conserved group of phosphatases featuring a protein tyrosine phosphatase domain. Nine members are characterized by an active phosphatase domain C(X) 5 R, dephosphorylating the D3 position of PtdIns(3)P and PtdIns(3,5)P2. Mutations in myotubularin genes result in human myopathies, and several neuropathies including X-linked myotubular myopathy and Charcot-Marie-Tooth type 4B. MTM1, MTMR6 and MTMR14 also contribute to Ca2+ signaling and Ca2+ homeostasis that play a key role in many MTM-dependent myopathies and neuropathies. Here we explore the evolving roles of MTM1/MTMRs, unveiling their influence on critical aspects of Ca2+ signaling pathways. • Myotubularin are lipid phosphatases involved in membrane trafficking and cytoskeletal organization. • Myotubularins are merging as regulators if Ca2+ handling molecules and modulators of Ca2+ homeostasis. • Mutations in myotubularins are associated with disruption of Ca2+ homeostasis. [ABSTRACT FROM AUTHOR]