Abstract: SA-PO216

Dynamin: A Potential Regulator of Actin-Microtubule Interplay in Podocytes

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology

Authors

  • Mukherjee, Kamalika, Massachusetts General Hospital, Charlestown, Massachusetts, United States
  • Gu, Changkyu, Massachusetts General Hospital, Charlestown, Massachusetts, United States
  • Sever, Sanja, Massachusetts General Hospital, Charlestown, Massachusetts, United States
Background

Podocytes are a critical component of the glomerular filtration unit. Structural and functional anomalies in podocytes have been implicated in renal diseases such as focal segmental glomerulosclerosis and diabetic nephropathy. Podocyte injury, dysfunction and loss are correlated with aberrations in cytoskeletal organization of these specialized cells. Microtubules and actin are the prevalent cytoskeletal components of major processes and foot processes in podocytes. We therefore sought to decipher the interplay between microtubules and actin in podocytes and identify regulatory proteins that may facilitate this interaction.

Methods

Immunocytochemistry was performed to detect changes in the cytoskeleton. Spin-down- and GTP hydrolysis- assays were used to assess dynamin and microtubule interaction. Microtubule polymerization and depolymerization were studied in an isolated system using fluorescence based assays.

Results

1. Microtubule-regulating drugs alter actin cytoskeleton in podocytes. 2. Actin active drugs reorganize microtubule network. 3. Dynamin-modulating small molecules alter both microtubules and actin organization in podocytes. 4. Microtubule depolymerization is initiated in the presence of dynamin. 5. Tubulin polymerization is inhibited by dynamin. 6. Dynamin-regulating small molecules, in the presence of dynamin, alter polymerization state of microtubules.

Conclusion

Small molecule mediated alteration of actin cytoskeleton culminates in reorganization of microtubule network and vice versa. These observations demonstrate that the two cytoskeletal proteins are involved in constant communication with each other in podocytes. Moreover, altering the oligomerization state of dynamin affects both microtubule- and actin- cytoskeleton, which indicates that dynamin may qualify as one of the regulators of actin-microtubule crosstalk. Dynamin’s ability to promote actin polymerization has already been documented. Our current findings show that dynamin oligomerizes on microtubule templates and induces its depolymerization. Additionally, tubulin polymerization into microtubules is inhibited by dynamin. Therefore, dynamin oligomerization affects the polymerization state of both actin and microtubules. Taken together, we provide evidence that dynamin may regulate the interplay between microtubules and actin in podocytes.

Funding

  • NIDDK Support