Biology Reference
In-Depth Information
CHAPTER FOUR
Actin Isoforms in Neuronal
Development and Function
Thomas R. Cheever * , James. M. Ervasti ** , 1
* Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
** Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota,
Minneapolis, MN, USA
1 Corresponding author: E-mail: jervasti@umn.edu
Contents
1. Introduction
158
2. NeuronalActinCytoskeleton
158
3. ActinIsoforms
159
3.1. ExpressioninNeuronsandtheNervousSystem
160
3.2. DistinctBiochemicalProperties
161
4. RegulationofActinIsoformsinNeuronalDevelopmentandFunction
162
4.1. TranscriptionalRegulation
163
4.2. PosttranscriptionalRegulation
164
4.3. PosttranslationalRegulationofActinIsoforms
166
5. RolesforActinIsoformsinNeuronalDevelopmentandFunction
168
5.1. ActinIsoformExpressionPatternsduringNeuronalDiferentiation
andBrainDevelopment 168
5.1.1. Temporal and Protein Level Regulation 168
5.1.2. Spatial Localization 170
5.2. RolesfortheLocalizationandLocalTranslationof β -Actin 174
5.2.1. Local β -Actin Translation in Growth Cone Guidance 174
5.2.2. Local Translation of β -Actin in Dendrites and Dendritic Spine Morphogenesis 181
6. InsightsintoActinIsoformFunctionsfromInVivoStudiesandHumanDiseases 184
6.1. NovelRolesfor β -ActinRevealedbyaCNS-Speciic β -ActinKnockoutMouse 185
6.1.1. Contributions of β -Actin to Actin Isoform Expression within the Brain
185
6.1.2. Restricted Roles for β -Actin in Mediating Brain Structure
186
6.1.3. β -Actin Contributes to the Proper Regulation of Select Behaviors
189
6.2. InsightfromZBP1KnockoutandHeterozygousMouseStudies
192
6.3. HumanNeurologicalDiseasesRelatedto β -and γ -Actin
194
6.3.1. Potential Role for β -Actin in Spinal Muscular Atrophy
194
6.3.2. Neurological Effects of Mutations in Human β - and γ -Actin
197
7. FutureDirections
198
7.1. MolecularandCellularStudies
199
7.2. InVivoStudies
200
8. ConcludingRemarks
202
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