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Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome

Standard

Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome. / Rao, Jia; Ashraf, Shazia; Tan, Weizhen; van der Ven, Amelie T; Gee, Heon Yung; Braun, Daniela A; Fehér, Krisztina; George, Sudeep P; Esmaeilniakooshkghazi, Amin; Choi, Won-Il; Jobst-Schwan, Tilman; Schneider, Ronen; Schmidt, Johanna Magdalena; Widmeier, Eugen; Warejko, Jillian K; Hermle, Tobias; Schapiro, David; Lovric, Svjetlana; Shril, Shirlee; Daga, Ankana; Nayir, Ahmet; Shenoy, Mohan; Tse, Yincent; Bald, Martin; Helmchen, Udo; Mir, Sevgi; Berdeli, Afig; Kari, Jameela A; El Desoky, Sherif; Soliman, Neveen A; Bagga, Arvind; Mane, Shrikant; Jairajpuri, Mohamad A; Lifton, Richard P; Khurana, Seema; Martins, Jose C; Hildebrandt, Friedhelm.

in: J CLIN INVEST, Jahrgang 127, Nr. 12, 01.12.2017, S. 4257-4269.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rao, J, Ashraf, S, Tan, W, van der Ven, AT, Gee, HY, Braun, DA, Fehér, K, George, SP, Esmaeilniakooshkghazi, A, Choi, W-I, Jobst-Schwan, T, Schneider, R, Schmidt, JM, Widmeier, E, Warejko, JK, Hermle, T, Schapiro, D, Lovric, S, Shril, S, Daga, A, Nayir, A, Shenoy, M, Tse, Y, Bald, M, Helmchen, U, Mir, S, Berdeli, A, Kari, JA, El Desoky, S, Soliman, NA, Bagga, A, Mane, S, Jairajpuri, MA, Lifton, RP, Khurana, S, Martins, JC & Hildebrandt, F 2017, 'Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome', J CLIN INVEST, Jg. 127, Nr. 12, S. 4257-4269. https://doi.org/10.1172/JCI94138

APA

Rao, J., Ashraf, S., Tan, W., van der Ven, A. T., Gee, H. Y., Braun, D. A., Fehér, K., George, S. P., Esmaeilniakooshkghazi, A., Choi, W-I., Jobst-Schwan, T., Schneider, R., Schmidt, J. M., Widmeier, E., Warejko, J. K., Hermle, T., Schapiro, D., Lovric, S., Shril, S., ... Hildebrandt, F. (2017). Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome. J CLIN INVEST, 127(12), 4257-4269. https://doi.org/10.1172/JCI94138

Vancouver

Rao J, Ashraf S, Tan W, van der Ven AT, Gee HY, Braun DA et al. Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome. J CLIN INVEST. 2017 Dez 1;127(12):4257-4269. https://doi.org/10.1172/JCI94138

Bibtex

@article{cee12cb71ca5441884d4def32ba42133,
title = "Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome",
abstract = "Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex. Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). These effects were reversed by overexpression of WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants. The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. Together, these results delineate a comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with alterations in the action of PLCE1, an established SRNS protein.",
keywords = "Actin-Related Protein 2-3 Complex/genetics, Cell Movement/genetics, Diglycerides/genetics, Female, Humans, Male, Microfilament Proteins/genetics, Mutation, Nephrotic Syndrome/congenital, Phosphoinositide Phospholipase C/genetics, Podocytes/metabolism, Pseudopodia/genetics",
author = "Jia Rao and Shazia Ashraf and Weizhen Tan and {van der Ven}, {Amelie T} and Gee, {Heon Yung} and Braun, {Daniela A} and Krisztina Feh{\'e}r and George, {Sudeep P} and Amin Esmaeilniakooshkghazi and Won-Il Choi and Tilman Jobst-Schwan and Ronen Schneider and Schmidt, {Johanna Magdalena} and Eugen Widmeier and Warejko, {Jillian K} and Tobias Hermle and David Schapiro and Svjetlana Lovric and Shirlee Shril and Ankana Daga and Ahmet Nayir and Mohan Shenoy and Yincent Tse and Martin Bald and Udo Helmchen and Sevgi Mir and Afig Berdeli and Kari, {Jameela A} and {El Desoky}, Sherif and Soliman, {Neveen A} and Arvind Bagga and Shrikant Mane and Jairajpuri, {Mohamad A} and Lifton, {Richard P} and Seema Khurana and Martins, {Jose C} and Friedhelm Hildebrandt",
year = "2017",
month = dec,
day = "1",
doi = "10.1172/JCI94138",
language = "English",
volume = "127",
pages = "4257--4269",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",

}

RIS

TY - JOUR

T1 - Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome

AU - Rao, Jia

AU - Ashraf, Shazia

AU - Tan, Weizhen

AU - van der Ven, Amelie T

AU - Gee, Heon Yung

AU - Braun, Daniela A

AU - Fehér, Krisztina

AU - George, Sudeep P

AU - Esmaeilniakooshkghazi, Amin

AU - Choi, Won-Il

AU - Jobst-Schwan, Tilman

AU - Schneider, Ronen

AU - Schmidt, Johanna Magdalena

AU - Widmeier, Eugen

AU - Warejko, Jillian K

AU - Hermle, Tobias

AU - Schapiro, David

AU - Lovric, Svjetlana

AU - Shril, Shirlee

AU - Daga, Ankana

AU - Nayir, Ahmet

AU - Shenoy, Mohan

AU - Tse, Yincent

AU - Bald, Martin

AU - Helmchen, Udo

AU - Mir, Sevgi

AU - Berdeli, Afig

AU - Kari, Jameela A

AU - El Desoky, Sherif

AU - Soliman, Neveen A

AU - Bagga, Arvind

AU - Mane, Shrikant

AU - Jairajpuri, Mohamad A

AU - Lifton, Richard P

AU - Khurana, Seema

AU - Martins, Jose C

AU - Hildebrandt, Friedhelm

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex. Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). These effects were reversed by overexpression of WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants. The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. Together, these results delineate a comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with alterations in the action of PLCE1, an established SRNS protein.

AB - Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex. Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). These effects were reversed by overexpression of WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants. The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. Together, these results delineate a comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with alterations in the action of PLCE1, an established SRNS protein.

KW - Actin-Related Protein 2-3 Complex/genetics

KW - Cell Movement/genetics

KW - Diglycerides/genetics

KW - Female

KW - Humans

KW - Male

KW - Microfilament Proteins/genetics

KW - Mutation

KW - Nephrotic Syndrome/congenital

KW - Phosphoinositide Phospholipase C/genetics

KW - Podocytes/metabolism

KW - Pseudopodia/genetics

U2 - 10.1172/JCI94138

DO - 10.1172/JCI94138

M3 - SCORING: Journal article

C2 - 29058690

VL - 127

SP - 4257

EP - 4269

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 12

ER -