Essential role of Cenexin1, but not Odf2, in ciliogenesis. Cell Cycle
Primary cilia are microtubule-based solitary sensing structures on the cell surface that play crucial roles in cell signaling and development. Abnormal ciliary function leads to various human genetic disorders, collectively known as ciliopathies. Outer dense fiber protein 2 (Odf2) was initially isolated as a major component of sperm-tail fibers. Subsequent studies have demonstrated the existence of many splicing variants of Odf2, including Cenexin1 (Odf2 isoform 9), which bears an unusual C-terminal extension. Strikingly, Odf2 localizes along the axoneme of primary cilia, whereas Cenexin1 localizes to basal bodies in cultured mammalian cells. Whether Odf2 and Cenexin1 contribute to primary cilia assembly by carrying out either concerted or distinct functions is unknown. By taking advantage of odf2 (-/-) cells lacking endogenous Odf2 and Cenexin1, but exogenously expressing one or both of these proteins, we showed that Cenexin1, but not Odf2, was necessary and sufficient to induce ciliogenesis. Furthermore, the Cenexin1-dependent primary cilia assembly pathway appeared to function independently of Odf2. Consistently, Cenexin1, but not Odf2, interacted with GTP-loaded Rab8a, localized to the distal/subdistal appendages of basal bodies, and facilitated the recruitment of Chibby, a centriolar component that is important for proper ciliogenesis. Taken together, our results suggest that Cenexin1 plays a critical role in ciliogenesis through its C-terminal extension that confers a unique ability to mediate primary cilia assembly. The presence of multiple splicing variants hints that the function of Odf2 is diversified in such a way that each variant has a distinct role in the complex cellular and developmental processes.
Available from: Heidi Hehnly
- "More recently, studies showed that these GTPases and other RE components interact directly with mother/older centriole appendage proteins. For example, Rab11 and Rab8 can both interact directly with the appendage protein, Cenexin (Chang et al., 2013; Hehnly et al., 2012). Rab11 also interacts with a vesicle-tethering complex , the exocyst, through the specific exocyst subunit, Sec15 (Gromley et al., 2005; Wu, Mehta, Pichaud, Bellen, & Quiocho, 2005). "
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ABSTRACT: For some time, it has been known that recycling endosomes (REs) are organized in a nebulous "pericentrosomal" region in interphase cells. However, the collective use of previously developed methods, including centrosome isolation, live cell imaging, and electron microscopy, suggested that there is much more going on between the centrosome and the RE than previously imagined. By exploiting these approaches, we uncovered novel roles of the centrosome in RE function and, conversely, novel roles for REs in centrosome function. We first found that REs dynamically localized to the centrosome throughout the cell cycle. More specifically, we found that REs interacted with appendages of the older centriole in interphase cells to control endosome recycling, and this interaction was governed by RE-machinery including the small GTPase Rab11. We next determined that REs carry centrosome proteins to spindle poles as part of the "centrosome maturation" process. Here we discuss the methods used and materials needed to complete these types of studies.
Methods in cell biology 09/2015; 130:47-58. DOI:10.1016/bs.mcb.2015.03.024 · 1.42 Impact Factor
Available from: William Y Tsang
- "Since Cep83 and Cep164 can recruit IFT proteins to the basal body and/or the transition zone, these results imply that distal appendage proteins, Ttbk2, CP110, and IFT proteins could functionally interact [43,45]. In addition to Ttbk2, the loss of a second serine/threonine kinase, MARK4, causes mis-localization of its interacting partner, Odf2, which is normally found at sub-distal appendages, and likewise, inhibits cilia formation by preventing the removal of CP110/Cep97 from the basal body (Figure 2) [46-48]. In light of recent findings that distal and sub-distal appendages are assembled independently of one another , these intriguing observations suggest that Ttbk2 and MARK4 activities might be necessary to modulate the molecular framework of distal and sub-distal appendages, respectively, ultimately leading to the destruction and removal of CP110 from the basal body. "
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ABSTRACT: Cilia are hair-like protrusions found at the surface of most eukaryotic cells. They can be divided into two types, motile and non-motile. Motile cilia are found in a restricted number of cell types, are generally present in large numbers, and beat in a coordinated fashion to generate fluid flow or locomotion. Non-motile or primary cilia, on the other hand, are detected in many different cell types, appear once per cell, and primarily function to transmit signals from the extracellular milieu to the cell nucleus. Defects in cilia formation, function, or maintenance are known to cause a bewildering set of human diseases, or ciliopathies, typified by retinal degeneration, renal failure and cystic kidneys, obesity, liver dysfunction, and neurological disorders. A common denominator between motile and primary cilia is their structural similarity, as both types of cilia are composed of an axoneme, the ciliary backbone that is made up of microtubules emanating from a mother centriole/basal body anchored to the cell membrane, surrounded by a ciliary membrane continuous with the plasma membrane. This structural similarity is indicative of a universal mechanism of cilia assembly involving a common set of molecular players and a sophisticated, highly regulated series of molecular events. In this review, we will mainly focus on recent advances in our understanding of the regulatory mechanisms underlying cilia assembly, with special attention paid to the centriolar protein, CP110, its interacting partner Cep290, and the various downstream molecular players and events leading to intraflagellar transport (IFT), a process that mediates the bidirectional movement of protein cargos along the axoneme and that is essential for cilia formation and maintenance.
Cilia 07/2013; 2(1):9. DOI:10.1186/2046-2530-2-9
Available from: Timothy Megraw
Cell cycle (Georgetown, Tex.) 03/2013; 12(6). DOI:10.4161/cc.24152 · 4.57 Impact Factor
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