An in vitro assay reveals a role for the diaphragm protein PV-1 in endothelial fenestra morphogenesis
An in vitro assay reveals a role for the diaphragm protein PV-1 in endothelial fenestra morphogenesis
Fenestrae are small pores in the endothelium of renal glomerular, gastrointestinal, and endocrine gland capillaries and are involved in the bidirectional exchange of molecules between blood and tissues. Although decades of studies have characterized fenestrae at the ultrastructural level, little is known on the mechanisms by which fenestrae form. We present the development of an in vitro assay in which rapid and abundant fenestra induction enables a detailed study of their biogenesis. Through the use of agents that stabilize or disassemble actin microfilaments, we show that actin microfilament remodeling is part of fenestra biogenesis in this model. Furthermore, by using a loss-of-function approach, we show that the diaphragm protein PV-1 is necessary for fenestral pore architecture and the ordered arrangement of fenestrae in sieve plates. Together, these data provide insight into the cell biology of fenestra formation and open up the future study of the fenestra to a combined morphological and biochemical analysis.
actin filaments, sieve plates, vegf, vascular permeability
16770-16775
Ioannidou, Sofia
6d9b2f58-168b-4bea-8d9e-06c6dd20f739
Deinhardt, Katrin
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Miotla, Jadwiga
fe45b779-ba6c-4bf0-8079-1ca83945cb01
Bradley, John
f50910e6-6cb0-41ae-932a-0181d967cc93
Cheung, Eunice
ad64776c-971a-4d7a-8d8f-bb9081232d1a
Samuelsson, Steven
2690fa9d-30f5-4e6f-b47e-29cd1bbef76c
Ng, Yin-Shan
37550673-fe32-4f14-aff8-2e8220616c58
Shima, David T.
a84b2872-6c95-46cc-9456-cc3063e02aa8
7 November 2006
Ioannidou, Sofia
6d9b2f58-168b-4bea-8d9e-06c6dd20f739
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Miotla, Jadwiga
fe45b779-ba6c-4bf0-8079-1ca83945cb01
Bradley, John
f50910e6-6cb0-41ae-932a-0181d967cc93
Cheung, Eunice
ad64776c-971a-4d7a-8d8f-bb9081232d1a
Samuelsson, Steven
2690fa9d-30f5-4e6f-b47e-29cd1bbef76c
Ng, Yin-Shan
37550673-fe32-4f14-aff8-2e8220616c58
Shima, David T.
a84b2872-6c95-46cc-9456-cc3063e02aa8
Ioannidou, Sofia, Deinhardt, Katrin, Miotla, Jadwiga, Bradley, John, Cheung, Eunice, Samuelsson, Steven, Ng, Yin-Shan and Shima, David T.
(2006)
An in vitro assay reveals a role for the diaphragm protein PV-1 in endothelial fenestra morphogenesis.
Proceedings of the National Academy of Sciences, 103 (45), .
(doi:10.1073/pnas.0603501103).
(PMID:17075074)
Abstract
Fenestrae are small pores in the endothelium of renal glomerular, gastrointestinal, and endocrine gland capillaries and are involved in the bidirectional exchange of molecules between blood and tissues. Although decades of studies have characterized fenestrae at the ultrastructural level, little is known on the mechanisms by which fenestrae form. We present the development of an in vitro assay in which rapid and abundant fenestra induction enables a detailed study of their biogenesis. Through the use of agents that stabilize or disassemble actin microfilaments, we show that actin microfilament remodeling is part of fenestra biogenesis in this model. Furthermore, by using a loss-of-function approach, we show that the diaphragm protein PV-1 is necessary for fenestral pore architecture and the ordered arrangement of fenestrae in sieve plates. Together, these data provide insight into the cell biology of fenestra formation and open up the future study of the fenestra to a combined morphological and biochemical analysis.
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Published date: 7 November 2006
Keywords:
actin filaments, sieve plates, vegf, vascular permeability
Organisations:
Centre for Biological Sciences
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Local EPrints ID: 349465
URI: http://eprints.soton.ac.uk/id/eprint/349465
ISSN: 0027-8424
PURE UUID: 5c9c7882-158d-480b-9f00-bf002feb20be
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Date deposited: 05 Mar 2013 14:28
Last modified: 15 Mar 2024 03:45
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Author:
Sofia Ioannidou
Author:
Jadwiga Miotla
Author:
John Bradley
Author:
Eunice Cheung
Author:
Steven Samuelsson
Author:
Yin-Shan Ng
Author:
David T. Shima
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