Date of Award

Summer 8-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Pharmaceutical Sciences

First Advisor

Surya M. Nauli

Second Advisor

Reza Mehvar

Third Advisor

Rennolds Ostrom

Fourth Advisor

Marco Bisoffi

Abstract

The primary cilium is a solitary cellular organelle that protrudes from the apical cell membrane. Findings on cilia-dependent mechanosenstation have shown that the primary cilium acts as a transducer of fluid-shear stress into intracellular signaling. Over recent years, studies in primary cilia have intensified after determining a causal relationship between dysfunctional primary cilia and cystic diseases. Along with its mechanosensory function, the primary cilium houses a variety of receptors, ion channels and transporter proteins. Studies in cilia biology have shown that primary cilia are coordinators of signaling pathways such as Hedgehog (Hh), Wnt, and platelet-derived growth factor (PDGF) pathways during development and tissue homeostasis. The primary cilium has been established as a mechano, chemo- and osmosensing unit that transmits extracellular cues to the cell, which supports the importance of the primary cilium. As an important organelle involved in sensory functions and signal transductions, we encompass methodology for measuring cilia signaling along with a study of pH sensing function and cAMP signaling dynamics in the cilium. Defects in the structure of cilia or protein complexes located in the primary cilia cause a variety of diseases. With increasing the knowledge of ciliary biology, we can strategize approaches to repair defective cilia. Here we try to contribute to understanding the complex dynamic pathways of the cilia and point to potential pathways in regulating ciliary structure and function.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Sunday, August 01, 2021

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