title: The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections.
abstract: Mical is a reduction-oxidation (redox) enzyme that functions as an unusual F-actin disassembly factor during Drosophila development. Although three Molecule interacting with CasL (MICAL) proteins exist in vertebrate species, their mechanism of action remains poorly defined and their role in vivo unknown. Here, we report that vertebrate MICAL-1 regulates the targeting of secretory vesicles containing immunoglobulin superfamily cell adhesion molecules (IgCAMs) to the neuronal growth cone membrane through its ability to control the actin cytoskeleton using redox chemistry, thereby maintaining appropriate IgCAM cell surface levels. This precise regulation of IgCAMs by MICAL-1 is essential for the lamina-specific targeting of mossy fibre axons onto CA3 pyramidal neurons in the developing mouse hippocampus in vivo. These findings reveal the first in vivo role for a vertebrate MICAL protein, expand the repertoire of cellular functions controlled through MICAL-mediated effects on the cytoskeleton, and provide insights into the poorly characterized mechanisms underlying neuronal protein cell surface expression and lamina-specific axonal targeting.
authors.affiliation: 1] Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands [2].
authors.forename: Eljo Y
authors.initials: EY
authors.lastname: Van Battum
authors.affiliation: 1] Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands [2] [3].
authors.forename: Rou-Afza F
authors.initials: RA
authors.lastname: Gunput
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lemstra
authors.affiliation: 1] Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands [2] Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands.
authors.forename: Ewout J N
authors.initials: EJ
authors.lastname: Groen
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Ka Lou
authors.initials: KL
authors.lastname: Yu
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: Youri
authors.initials: Y
authors.lastname: Adolfs
authors.affiliation: 1] Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands [2].
authors.forename: Yeping
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Yukata
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
mesh_terms: D000199:Actins / Q000502:physiology; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D023421:Models, Animal; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D010084:Oxidation-Reduction; D022142:Secretory Vesicles / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D000199:Actins; D015816:Cell Adhesion Molecules, Neuronal; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C507541:Mical1 protein, mouse; D006899:Mixed Function Oxygenases