Activity-Dependent Localization of Integrin Adhesion Complex Proteins in Dendritic Spines

Synapses function as the signal transmission sites for communication between adjacent neurons. Synaptic plasticity is a property of synapses through which their ability for signal transmission can be increased or decreased, and this is believed to underlie learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity in which persistent activation of the synapse results in a lasting enhancement of signal transmission. During LTP, the actin cytoskeleton of dendritic spines, which are the post-synaptic compartments of excitatory synapses, undergoes remodeling. Integrins, which are the main receptors in integrin adhesion complexes (IACs), are crucial for this remodeling. However, it is not clear which other IAC components are relevant to the process. To investigate protein components of IACs and their relevance in LTP, I selected a set of 15 core IAC proteins based on literature and the host lab’s prior data on their structural variability. I constructed neural expression vectors encoding these proteins with a fluorescent tag, transfected rat primary cortical neuron cultures with the vectors, induced chemical LTP with glycine, fixed the cultures 30 minutes after LTP induction, and imaged them. By measuring the fluorescent intensity of the fluorescent tag in dendritic spines and comparing it to the intensity in the dendritic shaft, I calculated a synaptic enrichment score for each protein. I found that several IAC proteins are enriched in dendritic spines prior to LTP induction and this enrichment is altered in response to LTP. I found that 13 out of the 15 IAC proteins were enriched in dendritic spines prior to LTP induction, suggesting a greater role in spine stability than previously thought. Furthermore, three of these proteins: α-actinin-1, palladin, and sorbin and SH3 domain-containing protein 2 (SORBS2), increased their synaptic enrichment after LTP induction. These three proteins are known to form a complex that is found in structures, like stress fibres, that are associated with mechanical contractile force generation and mechanotrasduction, suggesting that these processes may be relevant to LTP. This study provides an initial screen of IAC protein components in dendritic spines during LTP. It can serve as a starting point for more sophisticated approaches to elucidate the mechanistic roles of IAC proteins and their activity-dependent remodelling in dendritic spines. Altogether, highlighting the unexplored mechanical properties involved in synaptic plasticity.