MICAL-family proteins: Complex regulators of the actin cytoskeleton

Sai Srinivas Panapakkam Giridharan, Steven H Caplan

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Significance: The molecules interacting with CasL (MICAL) family members participate in a multitude of activities, including axonal growth cone repulsion, membrane trafficking, apoptosis, and bristle development in flies. An interesting feature of MICAL proteins is the presence of an N-terminal flavo-mono-oxygenase domain. This mono-oxygenase domain generates redox potential with which MICALs can either oxidize proteins or produce reactive oxygen species (ROS). Actin is one such protein that is affected by MICAL function, leading to dramatic cytoskeletal rearrangements. This review describes the MICAL-family members, and discusses their mechanisms of actin-binding and regulation of actin cytoskeleton organization. Recent Advances: Recent studies show that MICALs directly induce oxidation of actin molecules, leading to actin depolymerization. ROS production by MICALs also causes oxidation of collapsin response mediator protein-2, a microtubule assembly promoter, which subsequently undergoes phosphorylation. Critical Issues: MICAL proteins oxidize proteins through two mechanisms: either directly by oxidizing methionine residues or indirectly via the production of ROS. It remains unclear whether MICAL proteins employ both mechanisms or whether the activity of MICAL-family proteins might vary with different substrates. Future Directions: The identification of additional substrates oxidized by MICAL will shed new light on MICAL protein function. Additional directions include expanding studies toward the MICAL-like homologs that lack flavin adenine dinucleotide domains and oxidation activity.

Original languageEnglish (US)
Pages (from-to)2059-2073
Number of pages15
JournalAntioxidants and Redox Signaling
Volume20
Issue number13
DOIs
StatePublished - May 1 2014

Fingerprint

Actin Cytoskeleton
Actins
Molecules
Proteins
Reactive Oxygen Species
Oxygenases
Oxidation
Growth Cones
Flavin-Adenine Dinucleotide
Microtubules
Diptera
Methionine
Oxidation-Reduction
Depolymerization
Phosphorylation
Substrates
Organizations
Apoptosis
Cones
Membranes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

MICAL-family proteins : Complex regulators of the actin cytoskeleton. / Giridharan, Sai Srinivas Panapakkam; Caplan, Steven H.

In: Antioxidants and Redox Signaling, Vol. 20, No. 13, 01.05.2014, p. 2059-2073.

Research output: Contribution to journalReview article

Giridharan, Sai Srinivas Panapakkam ; Caplan, Steven H. / MICAL-family proteins : Complex regulators of the actin cytoskeleton. In: Antioxidants and Redox Signaling. 2014 ; Vol. 20, No. 13. pp. 2059-2073.
@article{90700ba8110d41a18d32a919f5450c4c,
title = "MICAL-family proteins: Complex regulators of the actin cytoskeleton",
abstract = "Significance: The molecules interacting with CasL (MICAL) family members participate in a multitude of activities, including axonal growth cone repulsion, membrane trafficking, apoptosis, and bristle development in flies. An interesting feature of MICAL proteins is the presence of an N-terminal flavo-mono-oxygenase domain. This mono-oxygenase domain generates redox potential with which MICALs can either oxidize proteins or produce reactive oxygen species (ROS). Actin is one such protein that is affected by MICAL function, leading to dramatic cytoskeletal rearrangements. This review describes the MICAL-family members, and discusses their mechanisms of actin-binding and regulation of actin cytoskeleton organization. Recent Advances: Recent studies show that MICALs directly induce oxidation of actin molecules, leading to actin depolymerization. ROS production by MICALs also causes oxidation of collapsin response mediator protein-2, a microtubule assembly promoter, which subsequently undergoes phosphorylation. Critical Issues: MICAL proteins oxidize proteins through two mechanisms: either directly by oxidizing methionine residues or indirectly via the production of ROS. It remains unclear whether MICAL proteins employ both mechanisms or whether the activity of MICAL-family proteins might vary with different substrates. Future Directions: The identification of additional substrates oxidized by MICAL will shed new light on MICAL protein function. Additional directions include expanding studies toward the MICAL-like homologs that lack flavin adenine dinucleotide domains and oxidation activity.",
author = "Giridharan, {Sai Srinivas Panapakkam} and Caplan, {Steven H}",
year = "2014",
month = "5",
day = "1",
doi = "10.1089/ars.2013.5487",
language = "English (US)",
volume = "20",
pages = "2059--2073",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "13",

}

TY - JOUR

T1 - MICAL-family proteins

T2 - Complex regulators of the actin cytoskeleton

AU - Giridharan, Sai Srinivas Panapakkam

AU - Caplan, Steven H

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Significance: The molecules interacting with CasL (MICAL) family members participate in a multitude of activities, including axonal growth cone repulsion, membrane trafficking, apoptosis, and bristle development in flies. An interesting feature of MICAL proteins is the presence of an N-terminal flavo-mono-oxygenase domain. This mono-oxygenase domain generates redox potential with which MICALs can either oxidize proteins or produce reactive oxygen species (ROS). Actin is one such protein that is affected by MICAL function, leading to dramatic cytoskeletal rearrangements. This review describes the MICAL-family members, and discusses their mechanisms of actin-binding and regulation of actin cytoskeleton organization. Recent Advances: Recent studies show that MICALs directly induce oxidation of actin molecules, leading to actin depolymerization. ROS production by MICALs also causes oxidation of collapsin response mediator protein-2, a microtubule assembly promoter, which subsequently undergoes phosphorylation. Critical Issues: MICAL proteins oxidize proteins through two mechanisms: either directly by oxidizing methionine residues or indirectly via the production of ROS. It remains unclear whether MICAL proteins employ both mechanisms or whether the activity of MICAL-family proteins might vary with different substrates. Future Directions: The identification of additional substrates oxidized by MICAL will shed new light on MICAL protein function. Additional directions include expanding studies toward the MICAL-like homologs that lack flavin adenine dinucleotide domains and oxidation activity.

AB - Significance: The molecules interacting with CasL (MICAL) family members participate in a multitude of activities, including axonal growth cone repulsion, membrane trafficking, apoptosis, and bristle development in flies. An interesting feature of MICAL proteins is the presence of an N-terminal flavo-mono-oxygenase domain. This mono-oxygenase domain generates redox potential with which MICALs can either oxidize proteins or produce reactive oxygen species (ROS). Actin is one such protein that is affected by MICAL function, leading to dramatic cytoskeletal rearrangements. This review describes the MICAL-family members, and discusses their mechanisms of actin-binding and regulation of actin cytoskeleton organization. Recent Advances: Recent studies show that MICALs directly induce oxidation of actin molecules, leading to actin depolymerization. ROS production by MICALs also causes oxidation of collapsin response mediator protein-2, a microtubule assembly promoter, which subsequently undergoes phosphorylation. Critical Issues: MICAL proteins oxidize proteins through two mechanisms: either directly by oxidizing methionine residues or indirectly via the production of ROS. It remains unclear whether MICAL proteins employ both mechanisms or whether the activity of MICAL-family proteins might vary with different substrates. Future Directions: The identification of additional substrates oxidized by MICAL will shed new light on MICAL protein function. Additional directions include expanding studies toward the MICAL-like homologs that lack flavin adenine dinucleotide domains and oxidation activity.

UR - http://www.scopus.com/inward/record.url?scp=84898483100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898483100&partnerID=8YFLogxK

U2 - 10.1089/ars.2013.5487

DO - 10.1089/ars.2013.5487

M3 - Review article

C2 - 23834433

AN - SCOPUS:84898483100

VL - 20

SP - 2059

EP - 2073

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 13

ER -