Sebastian Patzke, a post-doc in Trond Stokke’s laboratory at the Department of Radiation Biology at the Institute for Cancer Research, identified CSPP proteins as integral part of primary cilia required for cilia formation. The results are now in press in the journal Molecular Biology of the Cell (journal impact factor: 5.558).
Together with co-workers from the University of Massachusetts and the University of Michigan he reports that CSPP proteins are required for the efficient localization of its binding partner NPHP8/RPGRIP1L/FTM, a cilia protein required for Hh signaling found mutated in cerebello-oculo-renal syndrome type ciliopathies, to the base of the cilium. Yet, similar to the effects of ectopical expression of CSPP-L, cilia length increased in NPHP8 depleted cells, suggesting that CSPP-L recruits its own negative regulator to the ciliary base. These results not only define a new function for CSPP-L but also add to the understanding of NPHP8.
|Fig. text: Immunofluorescence staining of serum starved hTERT-RPE1 cells for CSPP-L (green) and the primary cilium (acetylated tubulin, red). CSPP-L is localized to the basal body (centrosome) and decorates the microtubule axoneme of the primary cilium.|
Primary cilia are "cellular antenna" that co-ordinate a series of signal transduction pathways (incl. Hh, Wnt, and PDGFRα pathways) impinging on cell polarity, cell cycle control and cell migration. Given the functional role of CSPP-L during cell division described earlier by us and others ( Patzke et al., 2005; Patzke et al., 2006; Asiedu et al., 2009) it will be interesting to investigate if similar or distinct protein complexes are involved in the spatiotemporally separated processes of ciliogenesis and cytokinesis. Furthermore, the importance of cilia dependent Hh signaling has been reported in certain skin and brain tumors (Toftgard, 2009). Since CSPP1 expression is found altered in certain carcinomas it will be important to elucidate which function of CSPP proteins contributes to cancer development or progression.
Asiedu,M., Wu,D., Matsumura,F., and Wei,Q. (2009). Centrosome/spindle pole-associated protein regulates cytokinesis via promoting the recruitment of MyoGEF to the central spindle. Mol. Biol. Cell 20, 1428-1440.
Patzke,S., Hauge,H., Sioud,M., Finne,E.F., Sivertsen,E.A., Delabie,J., Stokke,T., and Aasheim,H.C. (2005). Identification of a novel centrosome/microtubule-associated coiled-coil protein involved in cell-cycle progression and spindle organization. Oncogene 24, 1159-1173.
Patzke,S., Redick,S., Warsame,A., Murga-Zamalloa,C.A., Khanna,H., Doxsey,S.J., and Stokke,T. (2010). CSPP is a ciliary protein interacting with Nephrocystin 8 and required for cilia formation. Mol. Biol. Cell.
Patzke,S., Stokke,T., and Aasheim,H.C. (2006). CSPP and CSPP-L associate with centrosomes and microtubules and differently affect microtubule organization. J. Cell Physiol 209, 199-210.
Toftgard,R. (2009). Two sides to cilia in cancer. Nat. Med. 15, 994-996.
Patzke S, Redick S, Warsame A, Murga-Zamalloa CA, Khanna H, Doxsey S, Stokke T
CSPP Is a Ciliary Protein Interacting with Nephrocystin 8 and Required for Cilia Formation
Mol Biol Cell (in press)