Freeing the brake: Proliferation needs primary cilium to disassemble
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Review Freeing the brake: Proliferation needs primary cilium to disassemble PRIYADARSHINI HALDER1, SHILPA KHATUN1 and SHUBHRA MAJUMDER2* 1
Department of Life Sciences, Presidency University, Kolkata 700 073, India
2
Department of Life Sciences and School of Biotechnology, Presidency University, Kolkata 700 073, India *Corresponding author (Email, [email protected]) MS received 15 April 2020; accepted 24 August 2020
Primary cilia are non-motile, microtubule-based, antennae-like organelle that protrude out from the cell surface and perform sensory function or transduce physiological signals in majority of the vertebrate cells. Cilia are assembled on basal bodies that are transformed centrioles. The assembly-disassembly of primary cilia may pose an additional measure on regulating cell cycle in vertebrate cells. While primary cilia are commonly found in differentiated or quiescent cells that are not cycling, disassembly of primary cilia may promote re-entry of these cells into the mitotic cycle, and support proliferation. Many cancer tissues or cancer-derived cells exhibit loss of primary cilia. However, primary cilia may also promote tumorigenesis in some contexts through growth-promoting signalling. This review will shed light on recent advancements of temporal coordination of ciliary disassembly and cell cycle progression, with a focus on how cilia loss may support tumorigenesis in various epithelial cancers. Keywords.
Cell cycle; hedgehog signalling; primary cilia disassembly; proliferation; tumorigenesis
1. Introduction Eukaryotic cilia and flagella (these two terms can be used interchangeably) share similar basic structure as they both are microtubule-based, membrane-ensheathed tiny projections from the cell surface, and are assembled on basal bodies. Cilia are either motile or non-motile, which confer to motility or sensory functions. Motile cilia that are found in a multitude at specialized epithelial layers such as trachea, oviduct or ependyma regulate directional fluid flow, while sperm flagellum or flagella in lower eukaryotes provide swimming ability (Afzelius 2004). On the other hand, a non-motile primary cilium, present in the majority of vertebrate cells, functions as mechanosensors or chemosensors and transduces signalling pathways (Anvarian et al. 2019). A cilium consists of a microtubule (MT)-based axoneme assembled on a basal body that is a transformed centriole. A pair of centrioles, namely ‘mother’ and ‘daughter’, form the core of a http://www.ias.ac.in/jbiosci
centrosome, which is surrounded by c-tubulin rich pericentriolar material (PCM) that emanates and organizes the cytoskeletal microtubular network in vertebrate cells. Generally, primary cilia (PC) are assembled in quiescent or interphase cells and must disassemble before those cells enter mitosis. Thus, the ciliogenesis program is regulated by both positive and negative regulators. While mechanistic details of various steps of cilia assembly were vividly i
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