title: A role for the Golgi matrix protein giantin in ciliogenesis through control of the localization of dynein-2.
abstract: The correct formation of primary cilia is central to the development and function of nearly all cells and tissues. Cilia grow from the mother centriole by extension of a microtubule core, the axoneme, which is then surrounded with a specialized ciliary membrane that is continuous with the plasma membrane. Intraflagellar transport moves particles along the length of the axoneme to direct assembly of the cilium and is also required for proper cilia function. The microtubule motor, cytoplasmic dynein-2 mediates retrograde transport along the axoneme from the tip to the base; dynein-2 is also required for some aspects of cilia formation. In most cells, the Golgi lies adjacent to the centrioles and key components of the cilia machinery localize to this organelle. Golgi-localized proteins have also been implicated in ciliogenesis and in intraflagellar transport. Here, we show that the transmembrane Golgi matrix protein giantin (GOLGB1) is required for ciliogenesis. We show that giantin is not required for the Rab11-Rabin8-Rab8 pathway that has been implicated in the early stages of ciliary membrane formation. Instead we find that suppression of giantin results in mis-localization of WDR34, the intermediate chain of dynein-2. Highly effective depletion of giantin or WDR34 leads to an inability of cells to form primary cilia. Partial depletion of giantin or of WDR34 leads to an increase in cilia length consistent with the concept that giantin acts through dynein-2. Our data implicate giantin in ciliogenesis through control of dynein-2 localization.
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: David
authors.initials: D
authors.lastname: Asante
authors.forename: Lucy
authors.initials: L
authors.lastname: Maccarthy-Morrogh
authors.forename: Anna K
authors.initials: AK
authors.lastname: Townley
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Weiss
authors.forename: Kentaro
authors.initials: K
authors.lastname: Katayama
authors.forename: Krysten J
authors.initials: KJ
authors.lastname: Palmer
authors.forename: Hiroetsu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Westlake
authors.forename: David J
authors.initials: DJ
authors.lastname: Stephens
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002502:Centrioles / Q000235:genetics; D002923:Cilia / Q000378:metabolism* / Q000502:physiology; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; C543203:WDR34 protein, human; C087574:macrogolgin; D004398:Dyneins
keywords: Cilia; Dynein; Golgi
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