Latest articles. 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 ARP23 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 ARP23 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. Jia Rao, Shazia Ashraf, Weizhen Tan, Amelie T. Ven, Heon Yung Gee, Daniela A. PI3K-Akt_Pathways_with_a_role_in_Cancer.png/700px-PI3K-Akt_Pathways_with_a_role_in_Cancer.png' alt='Rheb Activation Of Mtor' title='Rheb Activation Of Mtor' />Braun, Krisztina Fehr, Sudeep P. George, Amin Esmaeilniakooshkghazi, Won Il Choi, Tilman Jobst Schwan, Ronen Schneider, Johanna Magdalena Schmidt, Eugen Widmeier, Jillian K. Warejko, Tobias Hermle, David Schapiro, Svjetlana Lovric, Shirlee Shril, Ankana Daga, Ahmet Nayir, Mohan Shenoy, Yincent Tse, Martin Bald, Udo Helmchen, Sevgi Mir, Afig Berdeli, Jameela A. Kari, Sherif El Desoky, Neveen A. Soliman, Arvind Bagga, Shrikant Mane, Mohamad A. Jairajpuri, Richard P., 2008 2009,. Lifton, Seema Khurana, Jose C. Martins, Friedhelm Hildebrandt. F1.medium.gif' alt='Rheb Activation Of Mtor' title='Rheb Activation Of Mtor' />, 2011 2013, c, ,. Templates Joomla Gratuits. Issuu is a digital publishing platform that makes it simple to publish magazines, catalogs, newspapers, books, and more online. Easily share your publications and get. PI3KAKTmTOR is one of the three major signalling pathways that have been identified as important in cancer.