Dendrite maintenance

Abstract

The structural maintenance of dendrite arbors and dendritic spines is crucial for proper brain function. Dendrite arbors and dendritic spines transition from dynamic plasticity to greater stability during maturation. Dendrite branches stabilize before dendritic spines to retain overall dendrite arbor integrity while preserving the ability to fine-tune synaptic connections. Nonetheless, shared signaling mechanisms exist to coordinate shaping and stabilization of both dendritic spines and dendrite arbors. Long-term dendrite arbor and dendritic spine stability is maintained by dynamic cytoskeletal elements that turn over quickly. This process is exquisitely controlled by small GTPases, kinases, and proteins that regulate actin and microtubule polymerization, stability, and turnover. These proteins collectively ensure the precise formation and balanced turnover of the actin and microtubule cytoskeletons to maintain dendritic spine and dendrite structure. In addition, cell surface adhesion receptors, including Eph receptors, immunoglobulin superfamily receptors, cadherins, and integrins, play important roles in dendritic spine formation and stability by signaling to cytoplasmic nonreceptor tyrosine kinases that mediate changes in cytoskeletal structure. The loss of dendritic spine and/or dendrite arbor stability in humans is a major contributing factor to normal aging and the pathology of psychiatric illnesses, neurodegenerative diseases, and stroke. In this review, we discuss the cellular and molecular mechanisms that differentially regulate dendritic spine and dendrite arbor stability, examine how these mechanisms interact functionally, and highlight how they become disrupted in different pathological states.