The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections

Eljo Y Van Battum, Rou-Afza F Gunput, Suzanne Lemstra, Ewout J N Groen, Ka Lou Yu, Youri Adolfs, Yeping Zhou, Casper C Hoogenraad, Yukata Yoshida, Melitta Schachner, Anna Akhmanova, R Jeroen Pasterkamp

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Article number4317
Number of pages17
JournalNature Communications
Volume5
DOIs
Publication statusPublished - Jul 2014

Keywords / Materials (for Non-textual outputs)

  • CELL-ADHESION MOLECULE
  • LAMINA-RESTRICTED PROJECTION
  • AXON GUIDANCE
  • DENTATE GYRUS
  • CLOSE HOMOLOG
  • RECOGNITION MOLECULES
  • SYNAPTIC SPECIFICITY
  • NEURONAL MIGRATION
  • MENTAL-RETARDATION
  • NEURAL DEVELOPMENT

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