Abstract
Nerve cell connections, formed in the developing brain of mammals, undergo a well-programmed process of maturation with changes in their molecular composition over time. The major structural element at the post-synaptic specialization is the actin cytoskeleton, which is composed of different populations of functionally distinct actin filaments. Previous studies, using ultrastructural and light imaging techniques have established the presence of different actin filament populations at the post-synaptic site. However, it remains unknown, how these different actin filament populations are defined and how their molecular composition changes over time. In the present study, we have characterized changes in a core component of actin filaments, the tropomyosin (Tpm) family of actin-associated proteins from embryonal stage to the adult stage. Using biochemical fractionation of mouse brain tissue, we identified the tropomyosin Tpm4.2 as the major post-synaptic Tpm. Furthermore, we found age-related differences in the composition of Tpms at the post-synaptic compartment. Our findings will help to guide future studies that aim to define the functional properties of actin filaments at different developmental stages in the mammalian brain.
Highlights
The actin cytoskeleton plays an integral role in the structural and functional maturation of neurons
The actin cytoskeleton plays an integral role at the synapse, and Tpms are known to generate distinct F-actin populations (Gunning et al, 2008; Gateva et al, 2017), there is limited characterization of the Tpm expression profile at the post-synaptic compartment
Via the biochemical fractionation of post-synaptic density (PSD) and the adherent sub-synaptic web material, we identified the agerelated expression of Tpm4.2 in the post-synaptic compartment in the mouse brain
Summary
The actin cytoskeleton plays an integral role in the structural and functional maturation of neurons. At central nervous system synapses, continuous remodeling of actin filaments (F-actin) is the basis for supporting changes required for learning and memory formation. The pre-synaptic actin cytoskeleton is involved in the trafficking and endocytosis of synaptic vesicles. The rich postsynaptic actin network is critical for the delivery and anchorage of various neurotransmitters and other molecules required for synaptic transmission. Within the post-synaptic compartment, the F-actin network can further be differentiated into three filament populations based on their distinct turnover rates (Honkura et al, 2008). The varying roles and organization of the synaptic actin
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