Costal2 Functions as a Kinesin-like Protein in the Hedgehog Signal Transduction Pathway

Shohreh F. Farzan, Manuel Ascano, Stacey K. Ogden, Matthieu Sanial, Amira Brigui, Anne Plessis, David J. Robbins

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The Hedgehog (Hh) signaling pathway initiates an evolutionarily conserved developmental program required for the proper patterning of many tissues [1]. Although Costal2 (Cos2) is a requisite component of the Hh pathway, its mechanistic role is not well understood. Because of its primary sequence, Cos2 was initially predicted to function as a kinesin-like protein [2]. However, evidence showing that Cos2 function might require kinesin-like properties has been lacking [2-6]. Thus, the prevailing dogma in the field is that Cos2 functions solely as a scaffolding protein [7, 8]. Here, we show that Cos2 motility is required for its biological function and that this motility may be Hh regulated. We show that Cos2 motility requires an active motor domain, ATP, and microtubules. Additionally, Cos2 recruits and transports other components of the Hh signaling pathway, including the transcription factor Cubitus interruptus (Ci). Drosophila expressing cos2 mutations that encode proteins that lack motility are attenuated in their ability to regulate Ci activity and exhibit phenotypes consistent with attenuated Cos2 function [9]. Combined, these results demonstrate that Cos2 motility plays an important role in its function, regulating the amounts and activity of Ci that ultimately interpret the level of Hh to which cells are exposed.

Original languageEnglish (US)
Pages (from-to)1215-1220
Number of pages6
JournalCurrent Biology
Volume18
Issue number16
DOIs
StatePublished - Aug 26 2008
Externally publishedYes

Keywords

  • CELLBIO
  • SIGNALING

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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    Farzan, S. F., Ascano, M., Ogden, S. K., Sanial, M., Brigui, A., Plessis, A., & Robbins, D. J. (2008). Costal2 Functions as a Kinesin-like Protein in the Hedgehog Signal Transduction Pathway. Current Biology, 18(16), 1215-1220. https://doi.org/10.1016/j.cub.2008.07.026