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Molecular mechanisms of dendrite stability

Key Points

  • Cytoskeletal structure is the main stabilizing determinant in dendritic spines and dendrite shafts.

  • Actin cytoskeletal regulators are essential for dendritic spine maintenance.

  • Adhesion receptor and neurotrophin receptor signalling to the cytoskeleton confers long-term dendritic spine stability.

  • Microtubules and their organizing proteins are key controllers of dendrite arbor stabilization.

  • Specific signalling mechanisms mediate crosstalk between dendritic spine and dendrite stabilization pathways.

  • Pathological events target dendritic spines and dendrite branch stabilization mechanisms.

Abstract

In the developing brain, dendrite branches and dendritic spines form and turn over dynamically. By contrast, most dendrite arbors and dendritic spines in the adult brain are stable for months, years and possibly even decades. Emerging evidence reveals that dendritic spine and dendrite arbor stability have crucial roles in the correct functioning of the adult brain and that loss of stability is associated with psychiatric disorders and neurodegenerative diseases. Recent findings have provided insights into the molecular mechanisms that underlie long-term dendrite stabilization, how these mechanisms differ from those used to mediate structural plasticity and how they are disrupted in disease.

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Figure 1: Dendrite branch and dendritic spine dynamics change during development.
Figure 2: Cytoskeletal structure in dendrites.
Figure 3: Cytoskeletal signalling pathways that stabilize spines.
Figure 4: Pathways that mediate crosstalk between dendritic spines and dendrite arbors.
Figure 5: Disruption of spine and dendrite stabilization mechanisms in disease.

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Acknowledgements

I apologize to those whose excellent work I could not cite owing to word and reference limits. I am grateful to members of my laboratory, especially M. Kerrisk, A. Levy, M. Omar and Y-C. Lin for critical feedback, and to three anonymous reviewers for helpful suggestions on content. Work in my laboratory is supported by US National Institutes of Health grants NS39475, CA133346, and multi-PI grant GM100411 (joint with T. Boggon).

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Koleske, A. Molecular mechanisms of dendrite stability. Nat Rev Neurosci 14, 536–550 (2013). https://doi.org/10.1038/nrn3486

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