A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes

Abstract

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.

Midbody-Localized Aquaporin Mediates Intercellular Lumen Expansion During Early Cleavage of an Invasive Freshwater Bivalve

“…This likely allows for a precise temporal and spatial control over the water efflux from each blastomere, since we observed no Dro-lt-AQP1 accumulation in other areas of the embryos’ cell membranes. Midbody remnants have been shown to influence multiple postmitotic processes, including lumenogenesis, cell proliferation, cell signalling, cell polarity and fate specification as well as the formation of polarized structures such as neurites and cilia ( Antanavičiūtė et al, 2018 ; Peterman and Prekeris, 2019 ; Labat-de-Hoz et al, 2021 ). As such, there is a noteworthy overlap with known roles of AQPs not only in lumenogenesis ( Huebert et al, 2002 ; Hashizume and Hieda, 2006 ; Ferrari et al, 2008 ; Khan et al, 2013 ), but also in the regulation of cell stemness and proliferation ( Galán-Cobo et al, 2016 ; Dajani et al, 2018 ; Jung et al, 2021 ).…”

The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

“…The components of the machinery for ciliary growth are recruited normally to the centrosome zone under those conditions but are unable to elongate the primary cilium correctly and, consequently, the remaining cilia are stunted [46]. This effect of MAL silencing seems to be due to deficient condensation of the centrosome-associated membranes needed to build the ciliary membrane [88,89]. The overexpression of tagged MAL in MDCK cells and in transgenic mice also gives rise to fewer, shortened cilia.…”

HaCaT cells as a model system to study primary cilia in keratinocytes

“…In extracellular pathway, the basal body, transformed from the mother centriole, docks at the apical surface of the cell prior to axoneme extension 22 . An absolute majority of PC in keratinocytes were in the ‘OUT’ stage, which is consistent with extracellular pathway being typically employed in the cilia formation of polarized epithelial cells 23 …”

“…22 An absolute majority of PC in keratinocytes were in the 'OUT' stage, which is consistent with extracellular pathway being typically employed in the cilia formation of polarized epithelial cells. 23 As the number of recognized ciliopathies continues to increase, the importance of ciliary models also rises. Even though keratinocytes do not become as highly and rapidly ciliated as cell lines frequently used in ciliary studies, such as hTERT-RPE1 cells, they are a better model for the study of skin ciliopathies.…”