The long-term goals of my laboratory are to understand the cellular and molecular events that underlie gamete interactions and cell-cell fusion during fertilization. We use the unicellular, biflagellated alga Chlamydomonas for our studies. During Chlamydomonas fertilization, the interacting mt+ and mt- gametes undergo the cell biological events that characterize fertilization in almost all organisms. These events include: specific recognition and adhesion between gametes of opposite sex; adhesion-induced signal transduction and gamete activation; and adhesion and fusion between specialized fusogenic sites on the plasma membranes of the two gametes. The objectives of this proposal are to characterize the cellular and molecular mechanisms of gamete fusion. One focus of our studies will be on the FUS1 protein, which is encoded by an mt+, gamete-specific gene previously shown to be essential for cell-cell fusion. New sequence analysis indicates that FUS1 exhibits similarity to bacterial adhesion proteins. We have characterized the endogenous FUS1 protein and determined that it is approximately 95 kD and is localized to a small patch of membrane at the unactivated mt+ mating structure before gamete activation. Within seconds after gamete activation, FUS1 becomes distributed over the entire surface of the newly formed fertilization tubule. In addition, we discovered that not only are fus1- gametes unable to undergo gamete fusion, but they also fail to undergo a newly identified, mating structure adhesion step, called gamete docking. Thus, much like proteins involved in viral fusion, FUS1 is essential both for plasma membrane binding and plasma membrane fusion. Our new reagents and bioassays, in conjunction with the ease of genetic, biochemical, and molecular genetic manipulations in Chlamydomonas, now make it possible to carry out a detailed analysis of gamete plasma membrane adhesion/fusion in Chlamydomonas.
Our specific aims are to characterize the cellular and molecular properties of adhesion and fusion proteins in mt+ gametes; to identify mt+ gamete-specific proteins required for adhesion and fusion; to examine the functional domains of FUS1; and to identify and characterize adhesion and fusion proteins in mt- gametes. Currently, the molecular mechanisms of gamete fusion are not understood in any organism. Understanding gamete fusion in Chlamydomonas should inform future studies on human reproduction.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Chin, Jean
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Sw Medical Center Dallas
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Feng, Juan; Dong, Xianchi; Pinello, Jennifer et al. (2018) Fusion surface structure, function, and dynamics of gamete fusogen HAP2. Elife 7:
Angrisano, Fiona; Sala, Katarzyna A; Da, Dari F et al. (2017) Targeting the Conserved Fusion Loop of HAP2 Inhibits the Transmission of Plasmodium berghei and falciparum. Cell Rep 21:2868-2878
Fédry, Juliette; Liu, Yanjie; Péhau-Arnaudet, Gérard et al. (2017) The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein. Cell 168:904-915.e10
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:
Liu, Yanjie; Pei, Jimin; Grishin, Nick et al. (2015) The cytoplasmic domain of the gamete membrane fusion protein HAP2 targets the protein to the fusion site in Chlamydomonas and regulates the fusion reaction. Development 142:962-71
Dresselhaus, Thomas; Snell, William J (2014) Fertilization: a sticky sperm protein in plants. Curr Biol 24:R164-6
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
Snell, William J (2012) Development. Plant gametes do fertilization with a twist. Science 338:1038-9
Liu, Yanjie; Misamore, Michael J; Snell, William J (2010) Membrane fusion triggers rapid degradation of two gamete-specific, fusion-essential proteins in a membrane block to polygamy in Chlamydomonas. Development 137:1473-81
Ellerman, Diego A; Pei, Jimin; Gupta, Surabhi et al. (2009) Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm. Mol Reprod Dev 76:1188-99

Showing the most recent 10 out of 13 publications