التفاصيل البيبلوغرافية
| العنوان: |
Sonic hedgehog receptors and their localization at the primary cilium |
| المؤلفون: |
Cholmondeley, Karen |
| المساهمون: |
Frederic Charron (Internal/Supervisor) |
| بيانات النشر: |
McGill University |
| سنة النشر: |
2013 |
| المجموعة: |
Theses Canada / Thèses Canada (Library and Archives Canada) |
| مصطلحات موضوعية: |
Biology - Cell |
| الوقت: |
Master of Science (Department of Medicine) |
| الوصف: |
The Sonic hedgehog (Shh) signalling pathway is crucial for developmental events such as neural tube patterning and cell proliferation in the cerebellum. Almost all vertebrate cell types possess a primary cilium, an immotile microtubule-based structure that is the site of Shh signalling. Ptch1 and Smo are negative and positive regulators of the Shh pathway whose localization at the primary cilium is Shh-dependent. Recently, it has been shown that Boc, Cdo and Gas1 are required co-receptors of Ptch1, however, it has yet to be discovered whether these co-receptors also re-locate to and from the cilium in response to Shh. Here we show that a sufficient level of Ptch1 is a minimum requirement for recruiting Boc and Gas1 to the primary cilium in the presence of a pathway agonist. Surprisingly Cdo is not recruited to the primary cilium with or without Ptch1, despite its similarity to Boc. Structure-function analysis of Ptch1 and Boc suggests that the cytoplasmic tail is an important domain for their ciliary localization. For Gas1, mutations in regions close to the second GFRα-like domain and GPI tail affect recruitment to the cilium with Ptch1. Finally, we show that the role of Boc and Gas1 at the primary cilium may be to facilitate the removal of Ptch1 in response to Shh ligand, leading to the release of Smo and pathway activation. Altogether, these results improve our understanding of upstream Shh signal transduction and might eventually aid in the development of therapies targeting Shh signalling in developmental disorders and cancers. ; La voie de signalisation Sonic hedgehog (Shh) est cruciale pour de nombreux processus développementaux tels que la spécification régionale du tube neural et la prolifération cellulaire dans le cervelet. Presque tous les types cellulaires chez les vertébrés possèdent un cil primaire, une structure immobile et microtubulaire qui est le site de la signalisation Shh. Ptch1 et Smo sont des régulateurs respectivement positifs et négatifs de la voie Shh et leur localisation au cil primaire ... |
| نوع الوثيقة: |
thesis |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Electronically-submitted theses.; http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119528Test |
| الإتاحة: |
http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119528Test |
| حقوق: |
All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| رقم الانضمام: |
edsbas.B75B1169 |
| قاعدة البيانات: |
BASE |
