An in Vitro Assay Reveals a Role for the Diaphragm Protein PV-1 in Endothelial Fenestra Morphogenesis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Nov 1

PMID 17075074

Citations 52

Authors

Sofia Ioannidou

Katrin Deinhardt

Jadwiga Miotla

John Bradley

Eunice Cheung

Steven Samuelsson

Yin-Shan Ng

David T Shima

Affiliations

Soon will be listed here.

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.

Citing Articles

Contribution of VEGF-B-Induced Endocardial Endothelial Cell Lineage in Physiological Versus Pathological Cardiac Hypertrophy.

Sultan I, Ramste M, Peletier P, Hemanthakumar K, Ramanujam D, Tirronen A Circ Res. 2024; 134(11):1465-1482.

PMID: 38655691 PMC: 11542978. DOI: 10.1161/CIRCRESAHA.123.324136.

Human Pluripotent Stem Cells Derived Endothelial Cells Repair Choroidal Ischemia.

Li M, Wang P, Huo S, Qiu H, Li C, Lin S Adv Sci (Weinh). 2023; 11(9):e2302940.

PMID: 38115754 PMC: 10916649. DOI: 10.1002/advs.202302940.

The unique structural and functional characteristics of glomerular endothelial cell fenestrations and their potential as a therapeutic target in kidney disease.

Finch N, Neal C, Welsh G, Foster R, Satchell S Am J Physiol Renal Physiol. 2023; 325(4):F465-F478.

PMID: 37471420 PMC: 10639027. DOI: 10.1152/ajprenal.00036.2023.

Understanding tumour endothelial cell heterogeneity and function from single-cell omics.

Zeng Q, Mousa M, Nadukkandy A, Franssens L, Alnaqbi H, Alshamsi F Nat Rev Cancer. 2023; 23(8):544-564.

PMID: 37349410 DOI: 10.1038/s41568-023-00591-5.

Intracellular Membrane Transport in Vascular Endothelial Cells.

Mironov A, Mironov A, Sanavio B, Krol S, Beznoussenko G Int J Mol Sci. 2023; 24(6).

PMID: 36982865 PMC: 10059831. DOI: 10.3390/ijms24065791.

References

Stan R, Ghitescu L, Jacobson B, Palade G . Isolation, cloning, and localization of rat PV-1, a novel endothelial caveolar protein. J Cell Biol. 1999; 145(6):1189-98. PMC: 2133139. DOI: 10.1083/jcb.145.6.1189. View

Stan R, Kubitza M, Palade G . PV-1 is a component of the fenestral and stomatal diaphragms in fenestrated endothelia. Proc Natl Acad Sci U S A. 1999; 96(23):13203-7. PMC: 23925. DOI: 10.1073/pnas.96.23.13203. View

Pino R, Essner E . Structure and permeability to ferritin of the choriocapillary endothelium of the rat eye. Cell Tissue Res. 1980; 208(1):21-7. DOI: 10.1007/BF00234169. View

Muallem S, Kwiatkowska K, Xu X, Yin H . Actin filament disassembly is a sufficient final trigger for exocytosis in nonexcitable cells. J Cell Biol. 1995; 128(4):589-98. PMC: 2199902. DOI: 10.1083/jcb.128.4.589. View

Lombardi T, Montesano R, Orci L . Phorbol ester induces diaphragmed fenestrae in large vessel endothelium in vitro. Eur J Cell Biol. 1987; 44(1):86-9. View

Simionescu M, Simionescu N, Palade G . Morphometric data on the endothelium of blood capillaries. J Cell Biol. 1974; 60(1):128-52. PMC: 2109128. DOI: 10.1083/jcb.60.1.128. View

Milici A, Furie M, Carley W . The formation of fenestrations and channels by capillary endothelium in vitro. Proc Natl Acad Sci U S A. 1985; 82(18):6181-5. PMC: 391016. DOI: 10.1073/pnas.82.18.6181. View

Reeves W, Kanwar Y, Farquhar M . Assembly of the glomerular filtration surface. Differentiation of anionic sites in glomerular capillaries of newborn rat kidney. J Cell Biol. 1980; 85(3):735-53. PMC: 2111461. DOI: 10.1083/jcb.85.3.735. View

Carpenter B, Lin Y, Stoll S, Raffai R, McCuskey R, Wang R . VEGF is crucial for the hepatic vascular development required for lipoprotein uptake. Development. 2005; 132(14):3293-303. DOI: 10.1242/dev.01902. View

10.

Thurston G, Baldwin A . Endothelial actin cytoskeleton in rat mesentery microvasculature. Am J Physiol. 1994; 266(5 Pt 2):H1896-909. DOI: 10.1152/ajpheart.1994.266.5.H1896. View

11.

Eriksson A, Cao R, Roy J, Tritsaris K, Wahlestedt C, Dissing S . Small GTP-binding protein Rac is an essential mediator of vascular endothelial growth factor-induced endothelial fenestrations and vascular permeability. Circulation. 2003; 107(11):1532-8. DOI: 10.1161/01.cir.0000055324.34758.32. View

12.

Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P . Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004; 165(1):35-52. PMC: 1618540. DOI: 10.1016/S0002-9440(10)63273-7. View

13.

Braet F, de Zanger R, Baekeland M, Crabbe E, Van Der Smissen P, Wisse E . Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells. Hepatology. 1995; 21(1):180-9. View

14.

Stan R . Multiple PV1 dimers reside in the same stomatal or fenestral diaphragm. Am J Physiol Heart Circ Physiol. 2003; 286(4):H1347-53. DOI: 10.1152/ajpheart.00909.2003. View

15.

Gong C, Stoletov K, Terman B . VEGF treatment induces signaling pathways that regulate both actin polymerization and depolymerization. Angiogenesis. 2005; 7(4):313-21. DOI: 10.1007/s10456-004-7960-2. View

16.

Jin E, Ghazizadeh M, Fujiwara M, Nagashima M, Shimizu H, Ohaki Y . Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma. Pathol Int. 2001; 51(9):691-700. DOI: 10.1046/j.1440-1827.2001.01264.x. View

17.

Bankston P, Pino R . The development of the sinusoids of fetal rat liver: morphology of endothelial cells, Kupffer cells, and the transmural migration of blood cells into the sinusoids. Am J Anat. 1980; 159(1):1-15. DOI: 10.1002/aja.1001590102. View

18.

ANDREWS P . Investigations of cytoplasmic contractile and cytoskeletal elements in the kidney glomerulus. Kidney Int. 1981; 20(5):549-62. DOI: 10.1038/ki.1981.176. View

19.

Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N . Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003; 111(5):707-16. PMC: 151905. DOI: 10.1172/JCI17423. View

20.

Bearer E, Orci L . Endothelial fenestral diaphragms: a quick-freeze, deep-etch study. J Cell Biol. 1985; 100(2):418-28. PMC: 2113429. DOI: 10.1083/jcb.100.2.418. View