title: A role for Tctex-1 (DYNLT1) in controlling primary cilium length.
abstract: The microtubule motor complex cytoplasmic dynein is known to be involved in multiple processes including endomembrane organization and trafficking, mitosis, and microtubule organization. The majority of studies of cytoplasmic dynein have focused on the form of the motor that is built around the dynein-1 heavy chain. A second isoform, dynein heavy chain-2, and its specifically associated light intermediate chain, LIC3 (D2LIC), are known to be involved in the formation and function of primary cilia. We have used RNAi in human epithelial cells to define the cytoplasmic dynein subunits that function with dynein heavy chain 2 in primary cilia. We identify the dynein light chain Tctex-1 as a key modulator of cilia length control; depletion of Tctex-1 results in longer cilia as defined by both acetylated tubulin labeling of the axoneme and Rab8a labeling of the cilia membrane. Suppression of dynein heavy chain-2 causes concomitant loss of Tctex-1 and this correlates with an increase in cilia length. Compared to individual depletions, double siRNA depletion of DHC2 and Tctex-1 causes an even greater increase in cilia length. Our data show that Tctex-1 is a key regulator of cilia length and most likely functions as part of dynein-2.
authors.affiliation: Cell Biology Laboratories, School of Biochemistry, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Krysten J
authors.initials: KJ
authors.lastname: Palmer
authors.forename: Lucy
authors.initials: L
authors.lastname: MacCarthy-Morrogh
authors.forename: Nicola
authors.initials: N
authors.lastname: Smyllie
authors.forename: David J
authors.initials: DJ
authors.lastname: Stephens
mesh_terms: D000704:Analysis of Variance; D056444:Axonemal Dyneins / Q000378:metabolism; D002460:Cell Line; D002923:Cilia / Q000378:metabolism / Q000502:physiology*; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism; D034622:RNA Interference
chemical_list: C099883:DYNC2H1 protein, human; C533376:DYNLT1 protein, human; C494847:LMNA protein, human; D034904:Lamin Type A; D056444:Axonemal Dyneins; D056445:Cytoplasmic Dyneins; D004398:Dyneins