Examine the Role of EB1, a Regulator of Microtubule Dynamics, in Cyst Formation in ADPKD
Abstract
FY21 PRMRP Topic Area: Polycystic Kidney Disease. Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder caused by mutations in polycystin-1 and polycystin-2 and is characterized by slow growing cysts and progressive loss of renal function. Genes responsible for ADPKD have been discovered more than 20 years ago, yet there is no cure, and the mechanism of cyst formation remains elusive. Our data suggest a novel mechanism by which loss of polycystin-1 leads to increased expression of end-binding protein 1 that promotes cyst formation in ADPKD by increasing microtubule dynamics. Microtubules play critical role in many vital processes that are defective in ADPKD such as maintenance of cell shape and polarity, cell signaling, and cell division. However, information on the role of microtubules in ADPKD is limited. Microtubules are dynamic structures that alternate between phases of growth and shortening, a process called microtubule dynamics, to meet cell needs. We found that microtubules are moving faster in ADPKD cells, which may contribute to cyst formation. In this application, we will determine how polycystin-1 regulates microtubule dynamics. Then, we will determine whether mebendazole, a drug approved by the U.S. Food and Drug Administration to treat anthelmintic infections that is known to slow down microtubule dynamics, will prevent cyst formation in ADPKD mice. This study could lead to identification of new mechanisms of cyst formation and new therapeutic targets.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210006
Entities
People
- Valeriu Cebotaru
Organizations
- United States Army
- University of Maryland, Baltimore