EHD1 mediates vesicle trafficking required for normal muscle growth and transverse tubule development.

Avery D Posey, Kaitlin E Swanson, Manuel G Alvarez, Swathi Krishnan, Judy U Earley, Hamid Band, Peter Pytel, Elizabeth M McNally, Alexis R Demonbreun

Developmental biology 2014 Mar 15

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EHD proteins have been implicated in intracellular trafficking, especially endocytic recycling, where they mediate receptor and lipid recycling back to the plasma membrane. Additionally, EHDs help regulate cytoskeletal reorganization and induce tubule formation. It was previously shown that EHD proteins bind directly to the C2 domains in myoferlin, a protein that regulates myoblast fusion. Loss of myoferlin impairs normal myoblast fusion leading to smaller muscles in vivo but the intracellular pathways perturbed by loss of myoferlin function are not well known. We now characterized muscle development in EHD1-null mice. EHD1-null myoblasts display defective receptor recycling and mislocalization of key muscle proteins, including caveolin-3 and Fer1L5, a related ferlin protein homologous to myoferlin. Additionally, EHD1-null myoblast fusion is reduced. We found that loss of EHD1 leads to smaller muscles and myofibers in vivo. In wildtype skeletal muscle EHD1 localizes to the transverse tubule (T-tubule), and loss of EHD1 results in overgrowth of T-tubules with excess vesicle accumulation in skeletal muscle. We provide evidence that tubule formation in myoblasts relies on a functional EHD1 ATPase domain. Moreover, we extended our studies to show EHD1 regulates BIN1 induced tubule formation. These data, taken together and with the known interaction between EHD and ferlin proteins, suggests that the EHD proteins coordinate growth and development likely through mediating vesicle recycling and the ability to reorganize the cytoskeleton. Copyright © 2014 Elsevier Inc. All rights reserved.

Citation

Avery D Posey, Kaitlin E Swanson, Manuel G Alvarez, Swathi Krishnan, Judy U Earley, Hamid Band, Peter Pytel, Elizabeth M McNally, Alexis R Demonbreun. EHD1 mediates vesicle trafficking required for normal muscle growth and transverse tubule development. Developmental biology. 2014 Mar 15;387(2):179-90