The long-term goals of my research are to understand the cellular and molecular properties of cilia/flagella that underlie their functions. In addition to being used for motility, these organelles are widely employed as sensors to communicate environmental and physiological cues to the cell. My laboratory uses the biflagellated green alga Chlamydomonas reinhardtii as a model system to study flagella. We are investigating two sensory/signaling pathways focused on these microtubule-filled organelles. One pathway, the regulated flagellar disassembly pathway, brings about flagellar disassembly when cells sense environmental conditions inappropriate for the presence of flagella. The second, the flagellar adhesion induced signaling pathway, activates gametes when they sense (by flagellar adhesion) the presence of a gamete of the opposite sex. We have discovered that a Chlamydomonas member of the aurora protein kinase family, CALK, is an essential effector in the flagellar disassembly pathway. We propose experiments to learn more about the role of CALK in regulated flagellar disassembly, including testing the idea that CALK directly or indirectly regulates intraflagellar transport. In the flagellar adhesion-induced signaling pathway we determined that a protein tyrosine kinase in flagella is activated by flagellar adhesion and that its substrate is a cGMP-dependent protein kinase. Moreover, we found that activation and functioning of the flagellar adhesion-induced pathway are critically dependent on intraflagellar transport. We propose experiments to learn more about the early steps in flagellar adhesion-induced signaling and the role of intraflagellar transport in the pathway. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM025661-26A1
Application #
6885632
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Anderson, Richard A
Project Start
1978-07-01
Project End
2008-08-31
Budget Start
2004-09-15
Budget End
2005-08-31
Support Year
26
Fiscal Year
2004
Total Cost
$374,400
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Cao, Muqing; Ning, Jue; Hernandez-Lara, Carmen I et al. (2015) Uni-directional ciliary membrane protein trafficking by a cytoplasmic retrograde IFT motor and ciliary ectosome shedding. Elife 4:
Haubrich, Brad A; Collins, Emily K; Howard, Alicia L et al. (2015) Characterization, mutagenesis and mechanistic analysis of an ancient algal sterol C24-methyltransferase: Implications for understanding sterol evolution in the green lineage. Phytochemistry 113:64-72
Pan, Junmin; Snell, William J (2014) Organelle size: a cilium length signal regulates IFT cargo loading. Curr Biol 24:R75-8
Cao, Muqing; Meng, Dan; Wang, Liang et al. (2013) Activation loop phosphorylation of a protein kinase is a molecular marker of organelle size that dynamically reports flagellar length. Proc Natl Acad Sci U S A 110:12337-42
Belzile, Olivier; Hernandez-Lara, Carmen I; Wang, Qian et al. (2013) Regulated membrane protein entry into flagella is facilitated by cytoplasmic microtubules and does not require IFT. Curr Biol 23:1460-5
Ning, Jue; Otto, Thomas D; Pfander, Claudia et al. (2013) Comparative genomics in Chlamydomonas and Plasmodium identifies an ancient nuclear envelope protein family essential for sexual reproduction in protists, fungi, plants, and vertebrates. Genes Dev 27:1198-215
Miller, Matthew B; Haubrich, Brad A; Wang, Qian et al. (2012) Evolutionarily conserved Delta(25(27))-olefin ergosterol biosynthesis pathway in the alga Chlamydomonas reinhardtii. J Lipid Res 53:1636-45
Luo, Minna; Cao, Muqing; Kan, Yinan et al. (2011) The phosphorylation state of an aurora-like kinase marks the length of growing flagella in Chlamydomonas. Curr Biol 21:586-91
Rohatgi, Rajat; Snell, William J (2010) The ciliary membrane. Curr Opin Cell Biol 22:541-6
Piao, Tian; Luo, Minna; Wang, Liang et al. (2009) A microtubule depolymerizing kinesin functions during both flagellar disassembly and flagellar assembly in Chlamydomonas. Proc Natl Acad Sci U S A 106:4713-8

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