Skip to main content

The NIMA-related kinases as regulators of ciliary assembly, disassembly, and length

Resource type
Thesis type
(Thesis) Ph.D.
Date created
2013-09-18
Authors/Contributors
Abstract
Cilia are microtubule-based, membrane-enclosed organelles that project from the surface of most eukaryotic cells. Cilia perform important signalling functions in development and homeostasis, and disruption of these functions in humans and other metazoans is associated with diseases known as ciliopathies. Previously, it was hypothesized that the NIMA-related kinases (Neks) evolved to coordinate ciliogenesis and ciliary resorption with the cell cycle. In this work, I examine the events surrounding pre-mitotic resorption in Chlamydomonas, and the roles of two Neks in ciliary regulation, thereby advancing our understanding of the mechanisms that regulate ciliogenesis, ciliary resorption, and ciliary length. Pre-mitotic ciliary resorption occurs to free the basal body to act as a spindle pole during mitosis, although little is known of the mechanisms or signals that regulate this event. Here, I show that pre-mitotic resorption culminates in a severing event that separates the basal body from the transition zone in Chlamydomonas. This severing may be essential for cell cycle progression in Chlamydomonas and other organisms. Mutations in mammalian Nek1 are associated with defective ciliogenesis and severe ciliopathies, and signalling to the nucleus may be important for the etiology of these ciliopathies. Here, I show that Nek1 cycles through the nucleus. Nek1 is therefore a candidate to transduce signals between the cilium and nucleus. Previous work demonstrated that RNAi of the Chlamydomonas Nek CNK2 caused a slight increase in flagellar length. I characterized a new cnk2-1 null mutant and discovered that it contributes to the regulation of flagellar resorption and length control by regulating the rate of flagellar disassembly. My work with cnk2-1 and a mutant strain defective in a second ciliary kinase, lf4-7, revealed that flagellar length is controlled by a feedback system, wherein rates of both flagellar assembly and disassembly are modulated when flagella are too long.
Document
Identifier
etd8064
Copyright statement
Copyright is held by the author.
Permissions
The author granted permission for the file to be printed and for the text to be copied and pasted.
Scholarly level
Supervisor or Senior Supervisor
Thesis advisor: Quarmby, Lynne
Download file Size
etd8064_LHilton.pdf 7.09 MB

Views & downloads - as of June 2023

Views: 9
Downloads: 2