title: The light chains of microtubule-associated proteins MAP1A and MAP1B interact with α1-syntrophin in the central and peripheral nervous system.
abstract: Microtubule-associated proteins of the MAP1 family (MAP1A, MAP1B, and MAP1S) share, among other features, a highly conserved COOH-terminal domain approximately 125 amino acids in length. We conducted a yeast 2-hybrid screen to search for proteins interacting with this domain and identified α1-syntrophin, a member of a multigene family of adapter proteins involved in signal transduction. We further demonstrate that the interaction between the conserved COOH-terminal 125-amino acid domain (which is located in the light chains of MAP1A, MAP1B, and MAP1S) and α1-syntrophin is direct and occurs through the pleckstrin homology domain 2 (PH2) and the postsynaptic density protein 95/disk large/zonula occludens-1 protein homology domain (PDZ) of α1-syntrophin. We confirmed the interaction of MAP1B and α1-syntrophin by co-localization of the two proteins in transfected cells and by co-immunoprecipitation experiments from mouse brain. In addition, we show that MAP1B and α1-syntrophin partially co-localize in Schwann cells of the murine sciatic nerve during postnatal development and in the adult. However, intracellular localization of α1-syntrophin and other Schwann cell proteins such as ezrin and dystrophin-related protein 2 (DRP2) and the localization of the axonal node of Ranvier-associated protein Caspr1/paranodin were not affected in MAP1B null mice. Our findings add to a growing body of evidence that classical MAPs are likely to be involved in signal transduction not only by directly modulating microtubule function, but also through their interaction with signal transduction proteins.
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Department of Biochemistry and Cell Biology, Vienna, Austria.
authors.forename: Heike
authors.initials: H
authors.lastname: Fuhrmann-Stroissnigg
authors.forename: Rainer
authors.initials: R
authors.lastname: Noiges
authors.forename: Luise
authors.initials: L
authors.lastname: Descovich
authors.forename: Irmgard
authors.initials: I
authors.lastname: Fischer
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Albrecht
authors.forename: Fatiha
authors.initials: F
authors.lastname: Nothias
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Froehner
authors.forename: Friedrich
authors.initials: F
authors.lastname: Propst
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012583:Schwann Cells / Q000378:metabolism; D000099149:Ezrin
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D000099149:Ezrin; C491322:Cntnap1 protein, mouse; C490547:MAP1A protein, mouse; C099589:dystrophin-related protein 2; C085284:microtubule-associated protein 1B; C091825:syntrophin alpha1