Costal2 functions as a kinesin-like protein in the hedgehog signal transduction pathway.
Costal2 functions as a kinesin-like protein in the hedgehog signal transduction pathway.
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DOI：
10.1016/j.cub.2008.07.026
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发表时间：
2008-08-26
期刊：
影响因子：
9.2
通讯作者：
Robbins, David J.
中科院分区：
文献类型：
--
作者：
Farzan, Shohreh F.;Ascano, Manuel, Jr.;Ogden, Stacey K.;Sanial, Matthieu;Brigui, Amira;Plessis, Anne;Robbins, David J.
The Hedgehog (Hh) signaling pathway initiates an evolutionarily conserved developmental program required for the proper patterning of many tissues. Costal2 (Cos2) is a requisite component of the Hh pathway, whose mechanistic role is not well understood. Cos2 was initially predicted, based on its primary sequence, to function as a microtubule-associated (MT) molecular motor. However, despite being identified over a decade ago, evidence showing that Cos2 function might require kinesin-like properties has for the most part been lacking. Thus the prevailing dogma in the field is that Cos2 functions solely as a scaffolding protein during Hh signal transduction. Here, we provide the first evidence 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), throughout the cell. 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. 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.
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