Editors' ChoiceCell Biology

Akt regulates primary cilium dynamics

Sci. Signal.  21 Jun 2016:
Vol. 9, Issue 433, pp. ec145
DOI: 10.1126/scisignal.aah3763

Primary cilia are important sensory organs for eukaryotic cells, and defects in the formation or function of these organelles cause diseases known as ciliopathies. During mitosis, the primary cilium is disassembled, and the basal body, which is a modified centriole that anchors the cilium, moves into the nucleus where it participates in spindle formation. Inversin (INVS) is a component of the primary cilia of kidney epithelial cells and relocalizes to the spindle poles during mitosis. Mutations in INVS cause nephronophthisis type II, a type of nephropathy. Suizu et al. found that INVS interacted with the kinase Akt in a yeast two-hybrid system and in cultured human cells. In vitro, Akt phosphorylated INVS on residues that were important for both INVS dimerization and for the interaction between Akt and INVS. Using various human cell lines, the authors showed that activated Akt was present at basal bodies and that activating Akt, either by treating the cells with platelet-derived growth factor AA (PDGF-AA) or expressing a constitutively active form of Akt, caused INVS to relocalize from the cilium to the basal body. This relocalization of INVS was reduced when the residues in INVS that were phosphorylated by Akt were mutated. The residues in INVS that were phosphorylated by Akt were also required for proper spindle axis orientation. Knocking down Akt by RNA interference reduced the average cilium length and decreased the number of cells that made a primary cilium. Cilium length was also reduced in mouse embryonic fibroblasts lacking Akt. In canine kidney cells, preventing Akt-mediated phosphorylation of INVS disrupted lumen formation in three-dimensional culture. Akt promotes cellular proliferation and can be activated or inhibited by many different growth-regulating pathways. These findings suggest that one mechanism through which Akt may influence cell proliferation is by affecting the proper function of the primary cilium or processes associated with disassembly of the primary cilium during mitosis, such as spindle formation.

F. Suizu, N. Hirata, K. Kimura, T. Edamura, T. Tanaka, S. Ishigaki, T. Donia, H. Noguchi, T. Iwanaga, M. Noguchi, Phosphorylation-dependent Akt–Inversin interaction at the basal body of primary cilia. EMBO J. 35, 1346–1363 (2016). [PubMed]

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