Microtubule molecular-motor proteins are key players in endocytosis, in vesicular trafficking, in mitosis and in cell growth and differentiation, as well as in ciliary motility. My laboratory is interested in the role of the motor proteins and their cargos in signal transduction events in these processes. Particularly interesting is the new information linking kinesin and dynein intraciliary transport (ICT) components to human diseases, including left-right asymmetry determination, primary ciliary dyskinesia (PCD), polycystic kidney disease (PKD), retinitis pigmentosa and perhaps to cancer. My laboratory is studying the role of the motor proteins in ICT and other processes by molecular genetic and structural techniques, including high resolution electron microscopy. We have also been interested in studying the control of dynein activity in the axonemal nanomachine during ciliary motion. Dynein activity can be functionally studied by nanotechnological and molecular engineering techniques including in vitro translocation assays using computer-assisted image analysis to measure the rate of movement along microtubules when ATP is added. The speed of microtubule translocation affects ciliary motility. We have identified controlling elements: a 29 kDa dynein regulatory light chain and a centrin binding arm.
Current projects include:
§ Signal transduction molecules as cargo in ICT.
§ Nanotechnology of axonemal sliding.
§ Cloning of dynein regulatory proteins.
§ Structural localization of components in the ciliary membrane and axoneme.
§ Vesicular transport by kinesins and cytoplasmic dynein.
§ cAMP and Ca2+ control of ciliary motility in wt and mutant cells.
Schneider, L., Clement, C.A, Teilman,S.C., Pazour, G.J., Hoffmann, E.K., Satir, P. and Christensen, S.T. (2005) PDGFR.signaling is regulated through the primary cilium in fibroblasts Current Biol. Current Biol.15:1861-1866.
Seetharam, R.N., Wada,Y., Ramachandran, S., Hess, H., and Satir, P. (2006) Long-term storage of bionanodevices by freezing and lyophilization. Lab on a Chip 6:1239-1242.
Satir, P. and Christensen, S.T. (2006) Overview of structure and function of mammalian cilia. Ann. Rev. Physiol. 69:14.1-14.24.
Christensen, S.T, Pedersen, L.B, Schneider, L, and Satir, P. (2007) Sensory cilia and integration of signal transduction in human health and diseases. Traffic 8:97-109.
Satir, P. (2007) Cilia Biology: Stop overeating now! Current Biol. 17: R963-R965
Satir, P., Guerra, C., and Bell, A. (2007) Evolution and persistence of the cilium. Cell Motil. Cytoskel.64: 906-913
Bell, A, Satir, P., Grimes, G. (2008) Mirror-imaged doublets of Tetrahymena pustulata:implications for the development of left-right asymmetry. Develop. Biol. 34:150-160.
Kiprilov, E., Awan, A, Velho, M., Christensen, S.T., Satir, P, Bouhassira, E.E, and Hirsch, R.E. (2008) Human embryonic stem cells in culture possess primary cilia with hedgehog signal machinery. J. Cell Biol. 180:897-904.
Satir, P. (2008) Primary cilia: integral to development and disease. Develop. Dynamics 237:1953-1954.
Seetharam, R. and Satir, P. (2008) Coordination of outer arm dynein activity along axonemal doublet microtubules. Cell Motil. & the Cytoskel.65:572-580.
Seetharam, R.N., Blum, A.S., Soto, C.M., Whitley, J.L, Sapsford, K.E., Chatterji, A., Johnson, J.E., Guerra, C., Satir, P., and Ratna, B.R. (2008) Long term storage of biotemplated materials for sensing applications. Nanotechnology 19:105504 (7pp)
Satir, P. and Christensen S.T. (2008) Structure and function of mammalian cilia Histochem. Cell Biol.129:687-693
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