Alternative titles; symbols
HGNC Approved Gene Symbol: SYDE1
Cytogenetic location: 19p13.12 Genomic coordinates (GRCh38): 19:15,107,401-15,114,974 (from NCBI)
Rho family small GTPases (see 165390) regulate many cellular activities, including cell cycle progress, actin polymerization, membrane trafficking, and cell migration. SYDE1 is a GTPase-activating protein (GAP) that inactivates RHO GTPases (Lo et al., 2017).
Using microarray analysis to identify genes regulated by the transcription factor GCM1 (603715) in BeWo31 trophoblast-like cells, Lo et al. (2017) identified human SYDE1. The deduced 735-amino acid protein has a central C2 domain and a C-terminal RhoGAP domain. Database analysis suggested variable but ubiquitous SYDE1 expression, with highest expression in placenta, followed by uterus, retina, adrenal gland, ovary, and skeletal muscle. Immunohistochemical analysis of human placenta detected colocalization of SYDE1 with GCM1 in first-trimester trophoblast cells of villus and cell columns, with strong SYDE1 expression in term extravillous trophoblasts.
Lo et al. (2017) reported that the SYDE1 gene maps to chromosome 19p13.12.
Using chromatin immunoprecipitation analysis and reporter gene assays, Lo et al. (2017) identified GCM1 response elements in the SYDE1 promoter region. Overexpression of SYDE1 in human JAR trophoblast-like cells enhanced cell migration, concomitant with dissolution of focal adhesions, presence of disorganized stress fibers, and increased filopodia. Rho activity decreased and CDC42 (116952) and RAC1 (602048) activity increased in SYDE1-knockdown JAR cells. Knockdown of SYDE1 also reduced cell migration and invasion in primary human villous cytotrophoblasts. Expression of SYDE2 reversed migration and invasion deficits in SYDE1-knockdown JAR cells.
Lo et al. (2017) found that Syde1 -/- mice appeared normal and were fertile. Pregnant Syde1 -/- females showed placental abnormalities, including abnormal vasculature in labyrinth layer, placental permeability, and apoptosis not found in wildtype females. Microarray analysis suggested that elevated Syde2 expression may compensate for loss of Syde1 function in pregnant Syde -/- mice.
Lo, H.-F., Tsai, C.-Y., Chen, C.-P., Wang, L.-J., Lee, Y.-S., Chen, C.-Y., Liang, C.-T., Cheong, M.-L., Chen, H. Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth: SYDE1 regulates placental cell migration and invasion. J. Path. 241: 324-336, 2017. [PubMed: 27917469] [Full Text: https://doi.org/10.1002/path.4835]