Neurexins and Neuroligins: Recent Insights from Invertebrates

Abstract

During brain development, each neuron must find and synapse with the correct pre-and postsynaptic partners. The complexity of these connections and the relatively large distances some neurons must send their axons to find the correct partners makes studying brain development one of the most challenging, and yet fascinating disciplines in biology. Furthermore, once the initial connections have been made, the neurons constantly remodel their dendritic and axonal arbours in response to changing demands. Neurexin and neuroligin are two cell adhesion molecules identified as important regulators of this process. The importance of these genes in the development and modulation of synaptic connectivity is emphasised by the observation that mutations in these genes in humans have been associated with cognitive disorders such as Autism spectrum disorders, Tourette syndrome and Schizophrenia. The present review will discuss recent advances in our understanding of the role of these genes in synaptic development and modulation, and in particular, we will focus on recent work in invertebrate models, and how these results relate to studies in mammals.

22q12.3 microduplication overlapping the LARGE gene as a male-only affected loci responsible for increasing the risk of autism spectrum disorder

“…290286 had a 630-kb duplication at chr22:33,440,702-34,073,409 and exhibited a phenotype of global developmental delay and delayed gross motor development. In addition, complex rearrangement or duplication may cause gene mutations, which lead to cognitive disorders, such as ASD if such genes are important in the development and modulation of synaptic connectivity (12). While sequencing the 15 exons of this gene did not identify any significant mutations, it is suggested that the duplication associated with ASD is more frequent in males.…”

Presynaptic morphogenesis, active zone organization and structural plasticity in Drosophila

“…In fact, mutations in many different synaptic signaling pathways and effector genes have been identified by genetic screens, revealing that synapse morphogenesis requires a complex conversation between motor neurons and muscle that requires a combination of secreted factors (particularly important BMP and Wnt-family members [18, 19]), synaptic adhesion molecule (e.g. FasiclinII, Neurexin and Neuroligan, Teneurins [20–22]), and extracellular matrix [23]. Although activity-dependent control of NMJ morphogenesis was discovered decades ago [5], the advent of a simple acute stimulation paradigm [11]** created an opportunity to study mechanisms required to initiate bouton formation.…”

Neural Cell Adhesion Molecules Belonging to the Family of Leucine-Rich Repeat Proteins

“…In addition, α-Neurexins contain fi ve sites for alternative splicing in the region encoding the ectodomain, two of which are also present in β-Neurexins. These splice sites enable the generation of multiple splice variants of both α-and β-Neurexins [reviewed in Craig and Kang ( 2007 ) and Knight et al ( 2011 )]. …”