Myospryn is a novel binding partner for dysbindin in muscle

J Biol Chem. 2004 Mar 12;279(11):10450-8. doi: 10.1074/jbc.M312664200. Epub 2003 Dec 19.

Abstract

Dysbindin is a coiled-coil-containing protein that was initially identified in a screen for dystrobrevin-interacting proteins. Recently, dysbindin has been shown to be involved in the biogenesis of lysosome-related organelles and is also a major schizophrenia susceptibility factor. Although dysbindin has been implicated in a number of different cellular processes, little is known about its function. To determine the function of dysbindin in muscle, we performed a yeast two-hybrid screen to identify potential interacting proteins. Here we show that dysbindin binds to a novel 413-kDa protein, myospryn, which is expressed in cardiac and skeletal muscle. The transcript encoding myospryn encompasses genethonin-3, a transcript that is down-regulated in muscle from Duchenne muscular dystrophy patients and stretch-responsive protein 553, which is up-regulated in experimental muscle hypertrophy. The C terminus of myospryn contains BBC, FN3, and SPRY domains in a configuration reminiscent of the tripartite motif protein family, as well as the dysbindin-binding site and a region mediating self-association. Dysbindin and myospryn co-immunoprecipitate from muscle extracts and are extensively co-localized. These data demonstrate for the first time that there are tissue-specific ligands for dysbindin that may play important roles in the different disease states involving this protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • DNA, Complementary / metabolism
  • Down-Regulation
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Muscle Proteins / chemistry*
  • Muscle Proteins / metabolism
  • Muscle Proteins / physiology*
  • Muscles / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Subcellular Fractions / metabolism
  • Tissue Distribution
  • Transfection
  • Two-Hybrid System Techniques
  • Up-Regulation
  • beta-Galactosidase / metabolism

Substances

  • Carrier Proteins
  • Cmya5 protein, mouse
  • DNA, Complementary
  • Dtnbp1 protein, mouse
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • RNA, Messenger
  • genethonin-3 protein, mouse
  • beta-Galactosidase

Associated data

  • GENBANK/AJ575748