Year: 2018
Type: dissertation
Abstract: Platelets are small, abundant blood cells involved in many processes. Loss of function of Neurobeachin-like 2 (NBEAL2) is causative for Gray Platelet Syndrome (GPS), where patient platelets lack the crucial secretory α-granules. Thus, NBEAL2 is required for α-granule formation in platelet precursor megakaryocytes, but the functions and interaction partners of this protein are largely unknown. Here, I verified VAMP-associated protein A (VAPA) as an NBEAL2-binding protein. Co-immunoprecipitation (Co-IP) experiments confirmed the NBEAL2-VAPA interaction, which was mapped to at least five atypical FFAT motifs located within the PH-BEACH domain of NBEAL2. Structural modeling and docking simulations implicated one motif, termed ncFFAT*, however, Co-IP experiments with individual acidic residues in ncFFAT* (E2218K and D2224K) suggested that these residues are not uniquely involved. Immunofluorescence microscopy of human megakaryocytes and megakaryocytic cells suggested a partial interaction of NBEAL2 and VAPA. These studies suggest that NBEAL2-VAPA interactions may facilitate platelet α-granule formation.
Source: TSpace (University of Toronto)
Author: Kevin To
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3035796333