Departments of Molecular and Human Genetics and Neuroscience, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States
Brooke Allen
Department of Biochemistry and Biophysics, Texas A&M University, College Station, United States
Ilya Mertsalov
Department of Biochemistry and Biophysics, Texas A&M University, College Station, United States
Pedro Monagas-Valentin
Department of Biochemistry and Biophysics, Texas A&M University, College Station, United States
Melissa Koff
Department of Biochemistry and Biophysics, Texas A&M University, College Station, United States
Sarah Baas Robinson
Complex Carbohydrate Research Center, University of Georgia, Athens, United States
Kazuhiro Aoki
Complex Carbohydrate Research Center, University of Georgia, Athens, United States
Raisa Veizaj
Translational Metabolic Laboratory, Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
Dirk J Lefeber
Translational Metabolic Laboratory, Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
Michael Tiemeyer
Complex Carbohydrate Research Center, University of Georgia, Athens, United States
Departments of Molecular and Human Genetics and Neuroscience, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States
Modification by sialylated glycans can affect protein functions, underlying mechanisms that control animal development and physiology. Sialylation relies on a dedicated pathway involving evolutionarily conserved enzymes, including CMP-sialic acid synthetase (CSAS) and sialyltransferase (SiaT) that mediate the activation of sialic acid and its transfer onto glycan termini, respectively. In Drosophila, CSAS and DSiaT genes function in the nervous system, affecting neural transmission and excitability. We found that these genes function in different cells: the function of CSAS is restricted to glia, while DSiaT functions in neurons. This partition of the sialylation pathway allows for regulation of neural functions via a glia-mediated control of neural sialylation. The sialylation genes were shown to be required for tolerance to heat and oxidative stress and for maintenance of the normal level of voltage-gated sodium channels. Our results uncovered a unique bipartite sialylation pathway that mediates glia-neuron coupling and regulates neural excitability and stress tolerance.
