Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina

Biochim Biophys Acta. 2011 Oct;1813(10):1883-92. doi: 10.1016/j.bbamcr.2011.05.015. Epub 2011 Jul 13.

Abstract

The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that all USH1 and 2 proteins in the eye and the inner ear are organized into protein networks by scaffold proteins. This has contributed essentially to our current understanding of the function of USH proteins and explains why defects in proteins of different families cause very similar phenotypes. We have previously shown that the USH1G protein SANS (scaffold protein containing ankyrin repeats and SAM domain) contributes to the periciliary protein network in retinal photoreceptor cells. This study aimed to further elucidate the role of SANS by identifying novel interaction partners. In yeast two-hybrid screens of retinal cDNA libraries we identified 30 novel putative interacting proteins binding to the central domain of SANS (CENT). We confirmed the direct binding of the phosphodiesterase 4D interacting protein (PDE4DIP), a Golgi associated protein synonymously named myomegalin, to the CENT domain of SANS by independent assays. Correlative immunohistochemical and electron microscopic analyses showed a co-localization of SANS and myomegalin in mammalian photoreceptor cells in close association with microtubules. Based on the present results we propose a role of the SANS-myomegalin complex in microtubule-dependent inner segment cargo transport towards the ciliary base of photoreceptor cells.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • COS Cells
  • Cattle
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytoskeletal Proteins
  • Humans
  • Macaca mulatta
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Protein Binding / physiology
  • Retina / metabolism*
  • Yeasts / genetics
  • Yeasts / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Muscle Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • PDE4DIP protein, human
  • USH1G protein, human