Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton

J Biol Chem. 2003 Dec 5;278(49):49031-43. doi: 10.1074/jbc.M308104200. Epub 2003 Sep 22.

Abstract

Tuba is a novel scaffold protein that functions to bring together dynamin with actin regulatory proteins. It is concentrated at synapses in brain and binds dynamin selectively through four N-terminal Src homology-3 (SH3) domains. Tuba binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain. Direct binding partners include N-WASP and Ena/VASP proteins. Forced targeting of the C-terminal SH3 domain to the mitochondrial surface can promote accumulation of F-actin around mitochondria. A Dbl homology domain present in the middle of Tuba upstream of a Bin/amphiphysin/Rvs (BAR) domain activates Cdc42, but not Rac and Rho, and may thus cooperate with the C terminus of the protein in regulating actin assembly. The BAR domain, a lipid-binding module, may functionally replace the pleckstrin homology domain that typically follows a Dbl homology domain. The properties of Tuba provide new evidence for a close functional link between dynamin, Rho GTPase signaling, and the actin cytoskeleton.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeleton / metabolism*
  • Dynamins / metabolism*
  • Immunohistochemistry
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Retroviridae Proteins, Oncogenic / metabolism*
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques

Substances

  • Actins
  • Cytoskeletal Proteins
  • DNMBP protein, human
  • Nerve Tissue Proteins
  • Retroviridae Proteins, Oncogenic
  • amphiphysin
  • Dynamins

Associated data

  • GENBANK/AY196211
  • GENBANK/AY383729