Control of neural circuit formation by leucine-rich repeat proteins

Abstract

The function of neural circuits depends on the precise connectivity between populations of neurons. Increasing evidence indicates that disruptions in excitatory or inhibitory synapse formation or function lead to excitation/inhibition (E/I) imbalances and contribute to neurodevelopmental and psychiatric disorders. Leucine-rich repeat (LRR)-containing surface proteins have emerged as key organizers of excitatory and inhibitory synapses. Distinct LRR proteins are expressed in different cell types and interact with key pre- and postsynaptic proteins. These protein interaction networks allow LRR proteins to coordinate pre- and postsynaptic elements during synapse formation and differentiation, pathway-specific synapse development, and synaptic plasticity. LRR proteins thus play a critical role in organizing synaptic connections into functional neural circuits, and their dysfunction may contribute to neuropsychiatric disorders.

Evolution of Protein Domain Repeats in Metazoa

“…Our results support this hypothesis. Repeats, particularly leucine-rich repeats (LRRs) and fibronectin repeats, have also been implicated in neural development in earlier studies (Dolan et al 2007; de Wit et al 2011; de Wit and Ghosh 2014). It has been observed that LRR families involved in neural development experienced many gene duplications in higher animals compared with worms (Dolan et al 2007) and that the number of repeat units in those families is highly variable (Dolan et al 2007).…”

Effect of ultrasounds on neurons and microglia: Cell viability and automatic analysis of cell morphology

“…Increasing evidence indicates that disruption in excitatory and inhibitory synapse formation and function, leads to excitation/inhibition imbalances and contributes to both neurodegenerative and neurodevelopmental disorders [18]. However, neuronal activity and connectivity by themselves provide an incomplete understanding of the onset and progression of neurodegenerative and neurodevelopmental diseases.…”

Lrig1 is a cell‐intrinsic modulator of hippocampal dendrite complexity and BDNF signaling

“…Distinct LRR protein families are highly enriched in the CNS, especially in the hippocampus, where they play a critical role in organizing synaptic connections into functional neural circuits. Given their crucial role in the organization of neuronal connectivity, it seems likely that dysfunctions in LRR genes or in their binding partners could compromise neuronal function and lead to neurodevelopmental and neuropsychiatric disorders [18].…”