Signaling through the primary cilium affects glial cell survival under a stressed environment

Abstract

Sensing extracellular milieu is a fundamental requirement of cells. To facilitate and specify sensory reception, mammalian cells develop an antenna-like structure denoted as the primary cilia. Nearly all interphase and nondividing cells in vertebrates have a single, nonmotile seemingly unspecialized cilium (called a primary cilium). In the central nervous system, astrocytes express primary cilia, but their function in astrocytes has not been examined. Recent studies have shown that primary cilia unite receptors and the machinery of signal-transduction components, such as Wnt and Hedgehog (Hh) signaling cascades. Although, Hh signaling cascades are known to be activated in various cells during development, their physiological functions in the adult nervous system, especially in glial cells, are still unknown. In this study, we reveal that glial primary cilia receive the Hh signal and regulate the survival of astrocytes under stressed conditions such as starvation. Interestingly, increased astrocyte survival was reversed by knockdown of Ift20, which is one of the main components for building primary cilia. These results collectively indicate that the activation of Hh signaling in the primary cilia plays an important role in the survival of astrocytes under stressed conditions.

Chemically inducible diffusion trap at cilia reveals molecular sieve–like barrier

“…We reasoned that the very initial flux of FKBP complexes across a proposed diffusion barrier into the cilium could be described by Fick's first law $$J=-D\frac{\left[F_{cy}\right]-\left[F_{ci}\right]}{x}$$ where [ F cy ] and [ F ci ] are concentrations of the FKBP construct in the cytoplasm and cilia, respectively, D is the diffusion coefficient of the FKBP construct, and x is the length of the diffusion barrier. We used equation (1) to solve for D for each construct using parameters derived from our experiments ([ F cy ] and J ), and structural details of primary cilia from our experiments and the literature 4, 20-23 ( Fig. 4a ).…”

Kinocilia Mediate Mechanosensitivity in Developing Zebrafish Hair Cells

“…This degeneration is surprising since mature auditory hair cells do not maintain kinocilia after development. It is therefore possible that calcium signals mediated by kinocilial-based mechanotransduction in immature cells may directly contribute to cell survival or initiate critical differentiation cues, two known important functions of primary cilia signaling in other contexts (Li et al, 2011; Yoshimura et al, 2011). …”

Detection of primary cilia in human glioblastoma

“…Primary cilia are non-motile, hair-like organelles that play a key role in promoting neural cell proliferation [5, 6], migration [7, 8], and survival [9] in the developing and adult CNS. Their ability to influence these important cellular events is linked to their ability to detect various mitogens [10, 11], neuropeptides [12], and secreted growth factors [13, 14] in the extracellular environment.…”