Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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