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The molecular composition of neuronal microfilaments is spatially and temporally regulated
R Weinberger1, G Schevzov, P Jeffrey
1Developmental Neurobiology Unit, Children's Medical Research Institute, Wentworthville, New South Wales, Australia.
Abstract:
The actin-based microfilament system is thought to play a critical role in neuronal development. We have determined specific changes in the composition of microfilaments accompanying neuronal morphogenesis. By using specific antibodies against the isoforms for tropomyosin (Tm) (Tm-5 and TmBr-1/-3) and actin (beta- and gamma-actin), we found that during early morphogenesis in vivo immature growing axons contain beta- and gamma-actin and Tm-5. In particular, Tm-5 is exclusively located in the immature axonal processes relative to the neuronal cell body. In contrast, beta-actin and Tm-5 are absent in mature, quiescent axons. This developmental loss from axons is associated with an approximately twofold downregulation of beta-actin and Tm-5 levels in the brain; gamma-actin levels do not change, and this molecule is widely distributed throughout neurons during development. The loss of beta-actin and Tm-5 from axons is accompanied by a progressive appearance of TmBr-1/-3. This apparent replacement of Tm-5 with TmBr-1/-3 occurs over a 2 d time period during rat embryonic hindbrain development and is conserved in evolution between birds and mammals. The loss of Tm-5 from axons involves a redistribution of this molecule to the cell soma and dendrites. These findings suggest that specialized microfilament domains are associated with the development and maintenance of neuronal polarity. We conclude that these Tm isoforms and beta-actin are subject to specific patterns of segregation associated with axonal development and neuronal differentiation. This provides a potential molecular basis for the temporal and spatial specificity of microfilament function during neuronal differentiation.
Insights
Neuronal development involves changes in actin and tropomyosin. Immature axons use beta-actin and Tm-5, which are replaced by TmBr-1/-3 in mature axons, suggesting specialized microfilaments for neuronal polarity.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The actin-based microfilament system is crucial for neuronal development.
- Specific changes in microfilament composition accompany neuronal morphogenesis.
Purpose of the Study:
- To determine specific changes in microfilament composition during neuronal morphogenesis.
- To investigate the roles of actin and tropomyosin isoforms in neuronal development and polarity.
Main Methods:
- Used specific antibodies against tropomyosin (Tm-5, TmBr-1/-3) and actin (beta-actin, gamma-actin) isoforms.
- Analyzed microfilament composition in developing and mature axons in vivo.
- Quantified protein levels in the brain during development.
Main Results:
- Immature axons contain beta- and gamma-actin and Tm-5, with Tm-5 localized to growing processes.
- Mature axons lack beta-actin and Tm-5, showing downregulation of these proteins.
- Beta-actin and Tm-5 are replaced by TmBr-1/-3 in axons during a 2-day period, conserved across species.
- Tm-5 redistributes to the cell soma and dendrites as axons mature.
Conclusions:
- Specific tropomyosin isoforms and beta-actin exhibit distinct segregation patterns during axonal development and neuronal differentiation.
- These molecular changes provide a basis for the temporal and spatial regulation of microfilament function in neurons.
- Specialized microfilament domains are associated with the development and maintenance of neuronal polarity.