PACSIN proteins bind tubulin and promote microtubule assembly

Exp Cell Res. 2008 Jun 10;314(10):1991-2003. doi: 10.1016/j.yexcr.2008.03.015. Epub 2008 Mar 29.

Abstract

PACSINs are intracellular adapter proteins involved in vesicle transport, membrane dynamics and actin reorganisation. In this study, we report a novel role for PACSIN proteins as components of the centrosome involved in microtubule dynamics. Glutathione S-transferase (GST)-tagged PACSIN proteins interacted with protein complexes containing alpha- and gamma-tubulin in brain homogenate. Analysis of cell lysates showed that all three endogenous PACSINs co-immunoprecipitated dynamin, alpha-tubulin and gamma-tubulin. Furthermore, PACSINs bound only to unpolymerised tubulin, not to microtubules purified from brain. In agreement, the cellular localisation of endogenous PACSIN 2 was not affected by the microtubule depolymerising reagent nocodazole. By light microscopy, endogenous PACSIN 2 localised next to gamma-tubulin at purified centrosomes from NIH 3T3 cells. Finally, reduction of PACSIN 2 protein levels with small-interfering RNA (siRNA) resulted in impaired microtubule nucleation from centrosomes, whereas microtubule centrosome splitting was not affected, suggesting a role for PACSIN 2 in the regulation of tubulin polymerisation. These findings suggest a novel function for PACSIN proteins in dynamic microtubuli nucleation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Brain / metabolism
  • Centrosome / metabolism*
  • Cytoskeletal Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Microtubules / metabolism*
  • NIH 3T3 Cells
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Tubulin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • PACSIN2 protein, human
  • Pacsin1 protein, mouse
  • Pacsin2 protein, mouse
  • Pacsin3 protein, mouse
  • Phosphoproteins
  • Protein Isoforms
  • Proteins
  • RNA, Small Interfering
  • Tubulin