A protective role for Drosophila Filamin in nephrocytes via Yorkie mediated hypertrophy
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A protective role for Drosophila Filamin in nephrocytes via Yorkie mediated hypertrophy. / Köhler, Sybille; Huber, Tobias; Denholm, Barry.
In: LIFE SCI ALLIANCE, Vol. 5, No. 12, e202101281, 03.08.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A protective role for Drosophila Filamin in nephrocytes via Yorkie mediated hypertrophy
AU - Köhler, Sybille
AU - Huber, Tobias
AU - Denholm, Barry
PY - 2022/8/3
Y1 - 2022/8/3
N2 - Podocytes are specialized epithelial cells of the kidney glomerulus and are an essential part of the filtration barrier. Because of their position, they are exposed to constant biomechanical forces such as shear stress and hydrostatic pressure. These forces increase during disease, resulting in podocyte injury. It is likely podocytes have adaptative responses to help buffer against deleterious mechanical force and thus reduce injury. However, these responses remain largely unknown. Here, using the Drosophila model, we show the mechanosensor Cheerio (dFilamin) provides a key protective role in nephrocytes. We found expression of an activated mechanosensitive variant of Cheerio rescued filtration function and induced compensatory and hypertrophic growth in nephrocytes depleted of the nephrocyte diaphragm proteins Sns or Duf. Delineating the protective pathway downstream of Cheerio we found repression of the Hippo pathway induces nephrocyte hypertrophy, whereas Hippo activation reversed the Cheerio-mediated hypertrophy. Furthermore, we find Yorkie was activated upon expression of active Cheerio. Taken together, our data suggest that Cheerio acts via the Hippo pathway to induce hypertrophic growth, as a protective response in abnormal nephrocytes.
AB - Podocytes are specialized epithelial cells of the kidney glomerulus and are an essential part of the filtration barrier. Because of their position, they are exposed to constant biomechanical forces such as shear stress and hydrostatic pressure. These forces increase during disease, resulting in podocyte injury. It is likely podocytes have adaptative responses to help buffer against deleterious mechanical force and thus reduce injury. However, these responses remain largely unknown. Here, using the Drosophila model, we show the mechanosensor Cheerio (dFilamin) provides a key protective role in nephrocytes. We found expression of an activated mechanosensitive variant of Cheerio rescued filtration function and induced compensatory and hypertrophic growth in nephrocytes depleted of the nephrocyte diaphragm proteins Sns or Duf. Delineating the protective pathway downstream of Cheerio we found repression of the Hippo pathway induces nephrocyte hypertrophy, whereas Hippo activation reversed the Cheerio-mediated hypertrophy. Furthermore, we find Yorkie was activated upon expression of active Cheerio. Taken together, our data suggest that Cheerio acts via the Hippo pathway to induce hypertrophic growth, as a protective response in abnormal nephrocytes.
U2 - 10.26508/lsa.202101281
DO - 10.26508/lsa.202101281
M3 - SCORING: Journal article
VL - 5
JO - LIFE SCI ALLIANCE
JF - LIFE SCI ALLIANCE
SN - 2575-1077
IS - 12
M1 - e202101281
ER -