Role of dynamin, synaptojanin, and endophilin in podocyte foot processes

Soda, Kunitsugu; Balkin, Daniel M.; Ferguson, Shawn M.; Paradise, Summer; Milošević, Ira; Giovedì, Silvia; Volpicelli‐Daley, Laura A.; Tian, Xuefei; Wu, Yumei; Ma, Hong; Son, Sung Hyun; Zheng, Rena; Moeckel, Gilbert; Cremona, Ottavio; Holzman, Lawrence B.; Camilli, Pietro De; Ishibe, Shuta

doi:10.1172/jci65289

Cited by 144 publications

(179 citation statements)

References 64 publications

Supporting

Mentioning

168

Contrasting

Order By: Relevance

“…There has been much speculation about the origin of these vesicles (36-39), but their functional significance has remained unresolved. Recent studies have demonstrated that impairment of the endocytic machinery in podocytes leads to proteinuria, indicating that endocytosis may play a crucial role in podocyte function (19,40,41). Our results reveal that podocytes induce significant levels of macropinocytosis in response to FFAs.…”

Section: Discussionsupporting

confidence: 54%

Albumin-associated free fatty acids induce macropinocytosis in podocytes

Chung¹,

Huber²,

Gödel³

et al. 2015

J. Clin. Invest.

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 54%

Albumin-associated free fatty acids induce macropinocytosis in podocytes

Chung¹,

Huber²,

Gödel³

et al. 2015

J. Clin. Invest.

View full text Add to dashboard Cite

“…31 Neither the CD pdKO mouse podocytes nor the podocytes of their CD Ctrl littermates displayed significant colocalization of podocin when tested with an early endosomal marker Rab5 (Supplemental Figure 2B). By contrast, a late endosomal marker for Rab7 was increased in CD pdKO mouse podocytes compared with CD Ctrl littermate podocytes ( Figure 8B, Supplemental Figures 2C and 3B).…”

Section: Subunit C Of Mitochondrial Atp Synthase Accumulated In Cdmentioning

confidence: 98%

Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD

Yamamoto-Nonaka

Koike²,

Asanuma

et al. 2016

JASN

View full text Add to dashboard Cite

Studies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte-specific CD-knockout mice that developed proteinuria at 5 months of age and ESRD by 20-22 months of age. Immunohistochemical analysis of these mice showed apoptotic podocyte death followed by proteinuria and glomerulosclerosis with aging. Using electron microscopy, we identified, in podocytes, granular osmiophilic deposits (GRODs), autophagosome/autolysosome-like bodies, and fingerprint profiles, typical hallmarks of CDdeficient neurons. CD deficiency in podocytes also led to the cessation of autolysosomal degradation and accumulation of proteins indicative of autophagy impairment and the mitochondrial ATP synthase subunit c accumulation in the GRODs, again similar to changes reported in CD-deficient neurons. Furthermore, both podocin and nephrin, two essential components of the slit diaphragm, translocated to Rab7-and lysosome-associated membrane glycoprotein 1-positive amphisomes/autolysosomes that accumulated in podocyte cell bodies in podocyte-specific CD-knockout mice. We hypothesize that defective lysosomal activity resulting in foot process effacement caused this accumulation of podocin and nephrin. Overall, our results suggest that loss of CD in podocytes causes autophagy impairment, triggering the accumulation of toxic subunit c-positive lipofuscins as well as slit diaphragm proteins followed by apoptotic cell death.

show abstract

“…39 Glomeruli were harvested and enriched from mice kidney cortical tissue with 45% Percoll solution (GE Healthcare BioSciences, Uppsala, Sweden) as previously described. 40 The kidneys were harvested immediately and washed in ice-cold Krebs-Henseleit saline solution (119 mM NaCl, 4.7 mM KCl, 1.9 mM CaCl 2 , 1.2 mM L KH 2 PO 4 , 1.2 mM MgSO 4 , 7H 2 O, and 25 mM NaHCO 3 , pH, 7.4).…”

Section: Cell Culturementioning

confidence: 99%

Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes

Hassan

Tian²,

Inoue³

et al. 2016

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Podocytes are terminally differentiated epithelial cells that reside along the glomerular filtration barrier. Evidence suggests that after podocyte injury, endoplasmic reticulum stress response is activated, but the molecular mechanisms involved are incompletely defined. In a mouse model, we confirmed that podocyte injury induces endoplasmic reticulum stress response and upregulated unfolded protein response pathways, which have been shown to mitigate damage by preventing the accumulation of misfolded proteins in the endoplasmic reticulum. Furthermore, simultaneous podocyte-specific genetic inactivation of X-box binding protein-1 (Xbp1), a transcription factor activated during endoplasmic reticulum stress and critically involved in the untranslated protein response, and Sec63, a heat shock protein-40 chaperone required for protein folding in the endoplasmic reticulum, resulted in progressive albuminuria, foot process effacement, and histology consistent with ESRD. Finally, loss of both Sec63 and Xbp1 induced apoptosis in podocytes, which associated with activation of the JNK pathway. Collectively, our results indicate that an intact Xbp1 pathway operating to mitigate stress in the endoplasmic reticulum is essential for the maintenance of a normal glomerular filtration barrier.

show abstract

Role of dynamin, synaptojanin, and endophilin in podocyte foot processes

Cited by 144 publications

References 64 publications

Albumin-associated free fatty acids induce macropinocytosis in podocytes

Albumin-associated free fatty acids induce macropinocytosis in podocytes

Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD

Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes

Contact Info

Product

Resources

About