The glomerular matrisome in Alport syndrome / Novel concepts of microtubule regulation during neuronal growth, maintenance and degeneration
| Dates: | 30 June 2015 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| How much: | Free |
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| Who is it for: | University staff |
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| Speaker: | Mike Randles, Ines Hahn |
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The glomerular matrisome in Alport syndrome:
The glomerular capillary wall is a highly sophisticated filtration barrier. Cell-matrix adhesion is essential for barrier integrity and ultimately for renal survival. Alport Syndrome results in renal failure and is caused by genetic defects in COL4A3, COL4A4 or COL4A5, but despite this knowledge there are currently no targeted therapies. We used proteomic and ultrastructural analysis to define the molecular landscape of cell-matrix adhesion in the glomerulus of Col4a3-/- (Alport) mice.
Novel concepts of microtubule regulation during neuronal growth, maintenance and degeneration:
Axons are very long, delicate structures that need to be maintained over decades. Parallel bundles of microtubules (MTs) form their structural backbones and transport highways. We study mechanisms of the MT regulating machinery in axons using versatile combinatorial genetics of Drosophila.
Spectraplakins guide polymerising microtubules along cortical F-actin, thereby laying axonal MTs out into parallel bundles. Here, we propose two novel mechanisms of local MT homeostasis: 1) A membrane-anchored cortical collapse factor serves as a check point by eliminating "off track" MTs that have escaped the guidance mechanism. 2) Axonal actin sustains the polymerisation of off-track MTs, thus counterbalancing MT collapse factor functions. Using super-resolution microscopy in combination with genetics, we have started to dissect actin network properties required for this function in neurons.
Our model of local MT homeostasis is novel and provides unprecedented understanding of mechanisms underlying axon longevity and degeneration.
Speakers
Mike Randles
Organisation: University of Manchester
Ines Hahn
Organisation: University of Manchester
Travel and Contact Information
Find event
Michael Smith Lecture Theatre
Michael Smith Building
Manchester
