|3D reconstruction model of all sensory cilia and associated glial cells in the amphid sensory organs in the C. elegans nose (from serial section transmission electron micrographs). From Doroquez, Berciu et al, eLife 2014 eLife|
Primary immotile cilia are microtubule-based organelles that have been referred to as cellular antennae. Although primary cilia were long thought to be present only on a subset of cells, it is now clear that nearly all eukaryotic cells are ciliated. Primary cilia house signaling molecules, and play critical roles in maintaining cellular functions in a broad range of cell types, including neurons in the mammalian peripheral and central nervous systems. The importance of cilia in regulating cellular homeostasis is highlighted by the finding that ciliary dysfunction underlies a plethora of disorders, now collectively termed ciliopathies. The overall goal of this project is to explore the mechanisms by which sensory cilia form and function, and how altered cilia function contributes to defects in sensory signaling, and consequently, animal development and behavior.
C. elegans is an established model organism for studying cilia formation and function. Unlike in mammals, only a subset of sensory neurons in C. elegans is ciliated, allowing us to study cilia function in defined cell types in vivo. These cilia house sensory signaling molecules and are absolutely essential for sensory signal transduction. Molecular mechanisms for ciliogenesis and cilia function are remarkably conserved from the blue-green alga Chlamydomonas to humans, allowing us to exploit the experimental power of C. elegans to understand how these important organelles form, and how they contribute to, and regulate, cellular functions. We have identified several new and conserved molecules required for sensory ciliogenesis, described new mechanisms of ciliary signaling protein trafficking, and used serial section electron microscopy and tomography to describe the 3D structures of individual sensory cilia at high resolution (in collaboration with Daniela Nicastro).
Members of the cilia squad are using genetic and molecular techniques, in vivo measurements of ciliary protein trafficking, electron microscopy, and functional assays to ask the following questions in C. elegans and cultured mammalian cells:
- How are the unique and complex morphologies of individual sensory neurons in C. elegans formed, and how do they contribute to sensory neuron function?
- How are ciliary proteins such as GPCRs and channels trafficked and localized to specific ciliary subcompartments?
- How does sensory signaling modulate cilia morphology?
- Can damaged cilia regenerate, and are the mechanisms different in young and aged animals?
- How is ciliogenesis coordinated with sensory neuron differentiation?
- Inna V. Nechipurenko, Anique Olivier-Mason, Anna Kazatskaya, Julie Kennedy, Ian G. McLachlan, Maxwell G. Heiman, Oliver E. Blacque, Piali Sengupta(2016) A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis Dev Cell http://dx.doi.org/10.1016/j.devcel.2016.07.013 [Pubmed]
- Brear, A.G., Yoon, J., Wojtnyiak, M. and Sengupta, P. (2014) Diverse cell-specific mechanisms localize G protein-coupled receptors to C. elegans sensory cilia. Genetics 2: 667-684. [PubMed]
- Doroquez DB*, Berciu C*, Anderson JR, Sengupta P, Nicastro D. (2014) A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in C. elegans. eLife. 2014;3:e01948. [PubMed]
- Wojtyniak M, Brear AG, O'Halloran DM, Sengupta P. (2013) Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans. J Cell Sci. 19: 4381-95. [PubMed]
- Olivier-Mason A, Wojtyniak M, Bowie RV, Nechipurenko IV, Blacque OE, Sengupta P. (2013) Transmembrane protein OSTA-1 shapes sensory cilia morphology via regulation of intracellular membrane trafficking in C. elegans. Development. 140: 1560-1572 [PubMed]
- Hall SE, Chirn GW, Lau NC, Sengupta P. (2013) RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans. RNA. 19: 306-19 [PubMed]
- Kaplan OI*, Doroquez DB*, Cevik S, Bowie RV, Clarke L, Sanders AA, Kida K, Rappoport JZ, Sengupta P, Blacque OE. (2012) Endocytosis genes facilitate protein and membrane transport in C. elegans sensory cilia. Curr Biol. 22: 451-60 [PubMed]