A new model for the structure and composition of the inversin compartment

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Abstract/Contents

Abstract
Primary cilia in many cell types contain a peri-axonemal sub-compartment called the inversin compartment. Four proteins have been found to assemble within the inversin compartment: INVS, ANKS6, NEK8, and NPHP3. The function of the inversin compartment is unknown but appears to be critical for normal development including left-right asymmetry and renal tissue homeostasis. Here we combine super-resolution imaging of human RPE1 cells, a classic model for studying primary cilia in vitro, with a genetic dissection of the protein-protein relationships important for compartment assembly to develop a new structural model. We propose that INVS is the core structural determinant of a compartment composed of novel fibril-like substructures which we identify here by 3D single-molecule super-resolution imaging. We find that NEK8 and ANKS6 depend on INVS for localization to the compartment, but NEK8-ANKS6 density within the compartment is intrinsically regulated by NEK8. Together NEK8 and ANKS6 are required downstream of INVS to localize and concentrate NPHP3 within the compartment. These results provide a more detailed structure for the inversin compartment and introduce a new example of a membrane-less compartment organized by protein-protein interactions

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2019; ©2019
Publication date 2019; 2019
Issuance monographic
Language English

Creators/Contributors

Author Bennett, Henrietta Wulsin
Degree supervisor Jackson, Peter K. (Peter Kent)
Thesis advisor Jackson, Peter K. (Peter Kent)
Thesis advisor Cimprich, Karlene
Thesis advisor Graves, Edward (Edward Elliot), 1974-
Thesis advisor Meyer, Tobias
Degree committee member Cimprich, Karlene
Degree committee member Graves, Edward (Edward Elliot), 1974-
Degree committee member Meyer, Tobias
Associated with Stanford University, Cancer Biology Program.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Henrietta Bennett
Note Submitted to the Cancer Biology Program
Thesis Thesis Ph.D. Stanford University 2019
Location electronic resource

Access conditions

Copyright
© 2019 by Henrietta Wulsin Bennett
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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