Alternative titles; symbols
HGNC Approved Gene Symbol: ABITRAM
Cytogenetic location: 9q31.3 Genomic coordinates (GRCh38): 9:108,934,400-108,950,744 (from NCBI)
ABITRAM is an actin-binding protein involved in the regulation of mobility and dendritogenesis of neurons (Derlig et al., 2014).
By screening databases, Derlig et al. (2013) identified ABITRAM, which they designated Simiate. Simiate is present a wide range of species including mammals, birds, reptiles, fish, insects, diverse invertebrates, and plants and protists, but it is eukaryotic and therefore absent from bacteria and archaea. Mouse Simiate is a small protein with a calculated molecular mass of 21.6 kD that contains several predicted consensus sequences for protein-protein interactions. Simiate mRNA contains several FMRP (FMR1; 309550) recognition motifs. A cluster of hydrophobic and acidic amino acids preceded by a small amino acid is distinctive for all Simiate orthologs. Western blot analysis revealed ubiquitous expression of Simiate at variable levels in mouse tissues, including brain. At the subcellular level, Simiate localized to somata and nuclear speckles.
Gross (2023) mapped the ABITRAM gene to chromosome 9q31.3 based on an alignment of the ABITRAM sequence (GenBank BC015795) with the genomic sequence (GRCh38).
By immunoprecipitation analysis, Derlig et al. (2013) showed that Simiate mRNA interacted with Fmr1 in mouse brain cytosolic extracts. Simiate and nuclear speckles were altered in Fmr1 -/- mouse brain, suggesting that loss of Fmr1 influenced expression of Simiate. Moreover, Simiate was essential for cell survival, as antibody inhibition of Simiate led to agglomeration of nuclear speckles and quickly induced apoptosis in HEK293 cells.
By immunoprecipitation and mass spectrometric analyses in mouse brain extracts, Derlig et al. (2014) showed that Simiate interacted directly with beta-actin (ACTB; 102630). Interaction with Simiate affected actin polymerization. Simiate and actin colocalized in lamellipodia and filopodia in HEK293 cells. By interacting with actin at these locations, Simiate affected mobility and environmental exploration of cells by regulating actin turnover. Analysis with cultured mouse hippocampal neurons suggested that Simiate regulation of actin dynamics was important for dendritogenesis. Interaction of Simiate and actin was important for differentiation of dendrites and arborization of neurons. Expression of Simiate in developing hippocampal neurons showed that Simiate specifically increased branching in proximal dendrites. Further analysis demonstrated that the effects of Simiate on cellular dynamics and arborization of neurons involved interaction with focal adhesion sites, as nuclear interactions involving Simiate and Fak (PTK2; 600758) were related to the function of Simiate in the organization of actin cytoskeleton.
Using heterologous expression systems and mouse brain extracts, Rama et al. (2022) showed that Simiate interacted specifically with both cytosolic and nuclear Fak1. Simiate associated with full-length Fak1 and the Fak80 fragment. In nucleus, Simiate showed a significant preference for Fak80. In mature neurons, Fak1 was most abundant in somata and dendrites, whereas Simiate was significantly enriched in nuclear speckles. However, during neuronal development, Fak1 and Simiate displayed significant variation in their levels of expression and colocalization in both nuclei and dendrites, indicating an involvement in dendritogenesis. Despite their colocalization and interaction, Fak1 and Simiate regulated distinct aspects of dendritogenesis, as the effects of Fak1 and Simiate depended on dendrite order and distance to the soma. Moreover, the proteins' effects on primary dendrites implied that they interacted to counterbalance each other to control dendrite formation. Mechanistically, Fak1 and Simiate colocalized in nuclear speckles and regulated transcriptional processes during dendritogenesis. In addition, stimulation by external signaling agents caused functional cooperation of Fak1 and Simiate in dendrites.
Derlig, K., Ehrhardt, T., Giessl, A., Brandstatter, J. H., Enz, R., Dahlhaus, R. Simiate is an actin binding protein involved in filopodia dynamics and arborization of neurons. Front. Cell. Neurosci. 8: 99, 2014. [PubMed: 24782708] [Full Text: https://doi.org/10.3389/fncel.2014.00099]
Derlig, K., Giessl, A., Brandstatter, J. H., Enz, R., Dahlhaus, R. Identification and characterisation of Simiate, a novel protein linked to the fragile X syndrome. PLoS One 8: e83007, 2013. [PubMed: 24349419] [Full Text: https://doi.org/10.1371/journal.pone.0083007]
Gross, M. B. Personal Communication. Baltimore, Md. 4/20/2023.
Rama, R., Derlig, K., Viessmann, N., Gossmann, R., Oriold, F., Giessl, A., Brandstatter, J. H., Enz, R., Dahlhaus, R. Simiate and the focal adhesion kinase FAK1 cooperate in the regulation of dendritogenesis. Sci. Rep. 12: 11274, 2022. [PubMed: 35787638] [Full Text: https://doi.org/10.1038/s41598-022-14460-y]