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Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals.

Membrane palmitoylated protein 4 (Mpp4) is a member of the membrane-associated guanylate kinase family. We show that Mpp4 localizes specifically to the plasma membrane of photoreceptor synaptic terminals. Plasma membrane Ca(2+) ATPases (PMCAs), the Ca(2+) extrusion pumps, interact with an Mpp4-dependent presynaptic membrane protein complex that includes Veli3 and PSD95. In mice lacking Mpp4, PMCAs were lost from rod photoreceptor presynaptic membranes. Synaptic ribbons were enlarged, a phenomenon known to correlate with higher Ca(2+). SERCA2 (sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase, type 2), which pumps cytosolic Ca(2+) into intracellular Ca(2+) stores and localizes next to the ribbons, was increased. The distribution of IP(3)RII (InsP(3) receptor, type 2), which releases Ca(2+) from the stores, was shifted away from the synaptic terminals. Synaptic transmission to second-order neurons was maintained but was reduced in amplitude. These data suggest that loss of Mpp4 disrupts a Ca(2+) extrusion mechanism at the presynaptic membranes, with ensuing adaptive responses by the photoreceptor to restore Ca(2+) homeostasis. We propose that Mpp4 organizes a presynaptic protein complex that includes PMCAs and has a role in modulating Ca(2+) homeostasis and synaptic transmission in rod photoreceptors.

Pubmed ID: 17341488


  • Yang J
  • Pawlyk B
  • Wen XH
  • Adamian M
  • Soloviev M
  • Michaud N
  • Zhao Y
  • Sandberg MA
  • Makino CL
  • Li T


Human molecular genetics

Publication Data

May 1, 2007

Associated Grants

  • Agency: NEI NIH HHS, Id: EY10309
  • Agency: NEI NIH HHS, Id: EY12944
  • Agency: NEI NIH HHS, Id: EY14104

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Calcium
  • Fluorescent Antibody Technique
  • Gene Deletion
  • Guanylate Kinase
  • Homeostasis
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Microscopy, Immunoelectron
  • Models, Biological
  • Multiprotein Complexes
  • Plasma Membrane Calcium-Transporting ATPases
  • Presynaptic Terminals
  • Protein Binding
  • Retinal Rod Photoreceptor Cells
  • Synaptic Transmission
  • Two-Hybrid System Techniques