title: The role of heparan sulfate deficiency in autistic phenotype: potential involvement of Slit/Robo/srGAPs-mediated dendritic spine formation.
abstract: Autism Spectrum Disorders (ASD) are the second most common developmental cause of disability in the United States. ASDs are accompanied with substantial economic and emotional cost. The brains of ASD patients have marked structural abnormalities, in the form of increased dendritic spines and decreased long distance connections. These structural differences may be due to deficiencies in Heparin Sulfate (HS), a proteoglycan involved in a variety of neurodevelopmental processes. Of particular interest is its role in the Slit/Robo pathway. The Slit/Robo pathway is known to be involved in the regulation of axonal guidance and dendritic spine formation. HS mediates the Slit/Robo interaction; without its presence Slit's repulsive activity is abrogated. Slit/Robo regulates dendritic spine formation through its interaction with srGAPs (slit-robo GTPase Activating Proteins), which leads to downstream signaling, actin cytoskeleton depolymerization and dendritic spine collapse. Through interference with this pathway, HS deficiency can lead to excess spine formation.
authors.affiliation: Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, 3515 E Fletcher Ave., Tampa, FL, 33613, USA. christine13@health.usf.edu.
authors.forename: Christine
authors.initials: C
authors.lastname: Pérez
authors.affiliation: Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, 3515 E Fletcher Ave., Tampa, FL, 33613, USA.
authors.forename: Darrell
authors.initials: D
authors.lastname: Sawmiller
authors.affiliation: Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, 3515 E Fletcher Ave., Tampa, FL, 33613, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006497:Heparan Sulfate / Q000172:deficiency*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D000097905:Roundabout Proteins
chemical_list: D020690:GTPase-Activating Proteins; D006497:Heparan Sulfate; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C492289:SLIT1 protein, human; C582067:SRGAP1 protein, human; C501995:SRGAP2 protein, human
keywords: Autism spectrum disorders; Axonal guidance; Dendritic spines; Glycosoaminoglycans; Heparan sulfate; Neurogenesis; Robo; Slit; Sulfotranferases; srGAPs