Loss of phosphatidylserine flippase β-subunit Tmem30a in podocytes leads to albuminuria and glomerulosclerosis

The asymmetric distribution of phosphatidylserine (PS) in the cytoplasmic leaflet of eukaryotic cell plasma membranes is regulated by a group of P4-ATPases (named PS flippases) and the β-subunit TMEM30A. Podocytes in the glomerulus form a filtration barrier to prevent the traversing of large cellula...

Full description

Saved in:
Bibliographic Details
Main Authors: Wenjing Liu (Author), Lei Peng (Author), Wanli Tian (Author), Yi Li (Author), Ping Zhang (Author), Kuanxiang Sun (Author), Yeming Yang (Author), Xiao Li (Author), Guisen Li (Author), Xianjun Zhu (Author)
Format: Book
Published: The Company of Biologists, 2021-06-01T00:00:00Z.
Subjects:
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!

MARC

LEADER 00000 am a22000003u 4500
001 doaj_6076f71152a94c08b98b3d6f224c4b6b
042 |a dc 
100 1 0 |a Wenjing Liu  |e author 
700 1 0 |a Lei Peng  |e author 
700 1 0 |a Wanli Tian  |e author 
700 1 0 |a Yi Li  |e author 
700 1 0 |a Ping Zhang  |e author 
700 1 0 |a Kuanxiang Sun  |e author 
700 1 0 |a Yeming Yang  |e author 
700 1 0 |a Xiao Li  |e author 
700 1 0 |a Guisen Li  |e author 
700 1 0 |a Xianjun Zhu  |e author 
245 0 0 |a Loss of phosphatidylserine flippase β-subunit Tmem30a in podocytes leads to albuminuria and glomerulosclerosis 
260 |b The Company of Biologists,   |c 2021-06-01T00:00:00Z. 
500 |a 1754-8403 
500 |a 1754-8411 
500 |a 10.1242/dmm.048777 
520 |a The asymmetric distribution of phosphatidylserine (PS) in the cytoplasmic leaflet of eukaryotic cell plasma membranes is regulated by a group of P4-ATPases (named PS flippases) and the β-subunit TMEM30A. Podocytes in the glomerulus form a filtration barrier to prevent the traversing of large cellular elements and macromolecules from the blood into the urinary space. Damage to podocytes can disrupt the filtration barrier and lead to proteinuria and podocytopathy. We observed reduced TMEM30A expression in patients with minimal change disease and membranous nephropathy, indicating potential roles of TMEM30A in podocytopathy. To investigate the role of Tmem30a in the kidney, we generated a podocyte-specific Tmem30a knockout (KO) mouse model using the NPHS2-Cre line. Tmem30a KO mice displayed albuminuria, podocyte degeneration, mesangial cell proliferation with prominent extracellular matrix accumulation and eventual progression to focal segmental glomerulosclerosis. Our data demonstrate a critical role of Tmem30a in maintaining podocyte survival and glomerular filtration barrier integrity. Understanding the dynamic regulation of the PS distribution in the glomerulus provides a unique perspective to pinpointing the mechanism of podocyte damage and potential therapeutic targets. 
546 |a EN 
690 |a tmem30a 
690 |a albuminuria 
690 |a focal segmental glomerulosclerosis 
690 |a glomerulosclerosis 
690 |a Medicine 
690 |a R 
690 |a Pathology 
690 |a RB1-214 
655 7 |a article  |2 local 
786 0 |n Disease Models & Mechanisms, Vol 14, Iss 6 (2021) 
787 0 |n http://dmm.biologists.org/content/14/6/dmm048777 
787 0 |n https://doaj.org/toc/1754-8403 
787 0 |n https://doaj.org/toc/1754-8411 
856 4 1 |u https://doaj.org/article/6076f71152a94c08b98b3d6f224c4b6b  |z Connect to this object online.