MICALs in control of the cytoskeleton, exocytosis, and cell death

MICALs form an evolutionary conserved family of multidomain signal transduction proteins characterized by a flavoprotein monooxygenase domain. MICALs are being implicated in the regulation of an increasing number of molecular and cellular processes including cytoskeletal dynamics and intracellular trafficking. Intriguingly, some of these effects are dependent on the MICAL monooxygenase enzyme and redox signaling, while other functions rely on other parts of the MICAL protein. Recent breakthroughs in our understanding of MICAL signaling identify the ability of MICALs to bind and directly modify the actin cytoskeleton, link MICALs to the docking and fusion of exocytotic vesicles, and uncover MICALs as anti-apoptotic proteins. These discoveries could lead to therapeutic advances in neural regeneration, cancer, and other diseases

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

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

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

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