Mechanistic basis of pannexin channel mechanosensitivity
| dc.contributor.author | Tanwar, Shubhamsingh | |
| dc.contributor.examiningcommittee | Anderson, Chris (Pharmacology & Therapeutics) Nagy, James (Physiology & Pathophysiology) | en_US |
| dc.contributor.supervisor | Jackson, Michael (Pharmacology & Therapeutics) | en_US |
| dc.date.accessioned | 2017-09-01T14:31:09Z | |
| dc.date.available | 2017-09-01T14:31:09Z | |
| dc.date.issued | 2017 | |
| dc.degree.discipline | Pharmacology and Therapeutics | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Pannexin1 (Panx1) forms membrane bound mechanosensitive ion channels and forms an integral component of various physiological and patho-physiological processes. It is well established that Panx1 responds to a wide range of mechanical stimuli. However, the mechanisms governing the mechanosensitivity are not known. My thesis investigates the mechanistic basis of Panx1 mechanosensitivity by employing whole cell voltage-clamp electrophysiology, along with biochemical, molecular and imaging techniques. The results demonstrate that the filamentous actin network regulates the (i) basal channel activity of Panx1 under iso-osmotic condition, (ii) augmentation of channel activity under the hypo-osmotic condition, and (iii) inhibition of channel activity under hyper-osmotic condition. Panx1 mechanosensitive responses are inhibited in cells expressing sequentially truncated Panx1 CT (356-414), suggesting that the Panx1 mechanosensitivity is conferred by the distal CT region. Data suggests that F-actin regulates Panx1 mechanosensitivity via interaction with distal Paxn1 CT using tethered mechanisms. | en_US |
| dc.description.note | October 2017 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/32411 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Pannexin | en_US |
| dc.subject | Mechanosensing | en_US |
| dc.subject | F-actin | en_US |
| dc.subject | Osmotic stress | en_US |
| dc.title | Mechanistic basis of pannexin channel mechanosensitivity | en_US |
| dc.type | master thesis | en_US |