Date of Graduation
School of Medicine
Microbiology, Immunology, and Cell Biology
Daniel C. Flynn.
Cellular motility and invasion in normal cellular processes and disease states such as cancer are dependent upon the ability of a cell to efficiently interact with its microenvironment, rearrange its cytoskeleton and degrade tissue barriers for purposes of cell movement. The AFAP family of adaptor proteins, AFAP1, AFAP1L1 and AFAP1L2, integrates signals received from the microenvironment into coordinated cytoskeletal changes. While there have been many reports on the functions and binding partners of AFAP1 and AFAP1L2, this work aimed to determine the cellular location and function of newly discovered AFAP1L1. The overall amino acid and protein structures of AFAP family members were compared so as to determine similarities and differences as well as to propose an evolutionary link between all three family members. As AFAP1 and AFAP1L1 have been shown to be more closely related, studies focused on a detailed comparison of these two family members. AFAP1 and AFAP1L1 were shown to have similar cellular localization in the cell by associating with stress filaments and cortical actin and also showing localization to invadosomes. Immunohistochemistry demonstrated differential expression of AFAP1L1 in the brain, particularly surrounding the Purkinje neurons, granular cells and neurons of the dentate nucleus. Although AFAP1 is a well known cSrc binding partner and activator, AFAP1L1 was determined to be a binding partner for cortactin, possibly through the SH3 domain. As other AFAP family members have been shown to be increased in various cancers, AFAP1L1 expression levels are upregulated in a number of cancers, particularly neuroblastoma and glioblastoma. While the similar amino acid sequence and modular domain identifies AFAP1L1 as a previously undescribed member of the AFAP family, the ability of AFAP1L1 to interact with cortactin and localize to distinct areas of the brain implies that AFAP1L1 has unique functions separate from AFAP1 and AFAP1L2.
Snyder, Brandi Nicole, "A New Member of the AFAP Family, AFAP1L1, Binds to Cortactin and Localizes to Invadosomes" (2011). Graduate Theses, Dissertations, and Problem Reports. 3379.