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MAGUK’s Protein Family

By Yona Bismuth, M.Sc.

An important family of membrane associated guanylate kinase proteins (MAGUK) are abundantly found in the brain. They are also called SAP (synapse associated proteins) because of their location at synapses. The four identified members of this family (PSD95, CHAPSYN110, SAP102, SAP97) have three similar domains (PDZ) at the N-terminus. At the C-terminus, they have one SH3 domain as well as a guanylate kinase-like sequence. PDZ (PSD95-Dlg-Zo-1) domains are found in hundreds of proteins in various cells and tissues. The archetype of the MAGUK family, PSD95, which is found in brain synapses, has been widely studied. Its X-ray structure shows a globular protein in which the C- and N-terminus are closed1,2. Studies reported interactions between a C-terminal tripeptide motif of T/SXV of NMDA receptor and PSD953,4,5 or other SAP proteins. It has also been shown that the binding of PSD95 to the C-terminus of Shaker K+ channels mediates their cell surface clustering. This clustering does not occur when PSD95 is missing6,7,8.

MAGUKs are found in submembraneous sites of post (PSD95) or presynaptic (SAP102, chapsyn110, SAP97) sides of the synapses.

This location, together with their interactions with signaling proteins suggests that they are involved in clustering of receptors or channels, formation of cellular junctions and organization of signaling pathways.

References

  1. Doyle, D.A. et al. (1996) Cell 85, 1067.
  2. Morais Cabral, J.H. et al. (1996) Nature 382, 649.
  3. Kornau, H.C. et al. (1995) Science 269, 1737.
  4. Niethammer, M. et al. (1996) J. Neurosci. 16, 2157.
  5. Lau, L.F. et al. (1996) J. Biol. Chem. 271, 21622.
  6. Kim, E. et al. (1996) Neuron 17, 103.
  7. Kim, E. et al. (1995) Nature 378, 85.
  8. Sheng, M. (1996) Neuron 17, 575.