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Thesis
CHARACTERIZING HS1-ASSOCIATED PROTEIN X-1'S (HAX1) ROLE IN REGULATING ARP2/3-HS1 INTERACTIONS IN NEUTROPHILS
University of West Florida
Master of Science (MS), University of West Florida
2018
Abstract
Neutrophils are the most abundant type of white blood cell and are part of the innate immune system. They are the first line of defense against fungal and bacterial infections. Dysfunctional neutrophils cause disorders in the immune system, including Kostmann syndrome, a severe congenital neutropenia, which is a life-threatening disease that affects 1 in 200,000 individuals. Persons with Kostmann syndrome have low peripheral neutrophil counts and develop life threatening infections. A loss-of-function mutation in the gene HAX1 has shown to cause Kostmann syndrome. HS1-associated protein X-1 (Hax1) was first discovered as a protein that interacts with HS1, a hematopoietic-specific actin-regulatory adapter protein important for actin assembly, branching, and filament stabilization. However, there remains a significant lack in understanding for Hax1 involvement in cytoskeletal rearrangement during chemotaxis that contributes to Kostmann syndrome. Specifically, it remains uncertain how Hax1 interacts with HS1 during cytoskeletal rearrangement and what regulates this interaction. By using a neutrophil model cell line (PLB-985), we can study neutrophil function and intracellular signaling via cell imaging, genetic manipulation, and biochemical analysis. Using PLB-985 cells deficient in Hax1 via shRNA knockdown, we found increased interaction between HS1 and arp2/3 via coimmunoprecipitation in the absence of fMLF relative to control shRNA expressing cells. The loss of Hax1 did not affect localization of HS1, arp2/3, and actin to the leading edge of neutrophils undergoing chemotaxis. These data suggest that Hax1 is a negative regulator of HS1- arp2/3 interactions.
Details
- Title
- CHARACTERIZING HS1-ASSOCIATED PROTEIN X-1'S (HAX1) ROLE IN REGULATING ARP2/3-HS1 INTERACTIONS IN NEUTROPHILS
- Resource Type
- Thesis
- Publisher
- University of West Florida
- Format
- text
- Copyright
- http://rightsstatements.org/vocab/InC-EDU/1.0/
- Identifiers
- 99380090729206600
- Academic Unit
- Biology
- Language
- English
- Awarding Institution
- University of West Florida; Master of Science (MS)
- Theses and Dissertations
- Master of Science (MS), University of West Florida