Biology subjects

Aitken, R.

Publications and source records attributed to Aitken, R..

3 recordsLinked to original sources

bioRxiv2026

Nanoarchitecture of the presynaptic cell adhesion molecule PTPσ in relation to prospective vesicle fusion sites and postsynaptic NMDA receptors

Protein organization at individual synapses tunes synaptic function. Presynaptic release-regulating proteins and postsynaptic receptors each concentrate into subsynaptic nanoclusters, and their precise alignment across the cleft into nanocolumns can maximize receptor activation following vesicle fusion. However, both the molecular organization defining presynaptic fusion sites and the mechanisms by which they are spatially coordinated with postsynaptic complexes remains unclear. Presynaptic transmembrane cell adhesion molecules may mediate both processes as they could simultaneously anchor cytosolic fusion machinery to the presynaptic membrane and bridge the cleft to coordinate PSD organization. The LAR-RPTP family member PTP{sigma} is an important possibility, as its trans-synaptic interactors that bind PSD-95 are associated with NMDAR dysfunction, suggesting PTP{sigma} may coordinate NMDAR positioning. However, PTP{sigma}'s subsynaptic organization has not been determined. Here, we investigate the cellular expression and subsynaptic nano-organization of endogenous PTP{sigma} in cultured rat hippocampal neurons. We find that PTP{sigma} is enriched at most excitatory synapses, but unexpectedly, PTP{sigma} nanoclusters do not colocalize with the vesicle priming protein Munc13-1. Instead, they adopt a stereotyped position adjacent to this machinery, without preferential association with sites in nanocolumns. PTP{sigma} nanoclusters also lie offset from postsynaptic NMDA receptors, mirroring their relationship to vesicle fusion sites, yet the presence of PTP{sigma} at a nanocolumn does not predict NMDAR abundance. Together, these findings suggest that PTP{sigma} does not directly coordinate release site - NMDAR alignment but instead occupies defined nanoscale positions adjacent to vesicle fusion sites, potentially helping to shape or stabilize the vesicle priming landscape of the active zone.

neuroscience↗

bioRxiv2026

Decoding human sperm signalling: Phosphoproteomic discovery of kinases governing fertilization competency

Capacitation, the process whereby sperm gain the functional competence to fertilize an egg in the absence of de novo transcription and translation, is orchestrated by a hierarchy of kinases driving the phosphorylation of sperm proteins. While increased phosphorylation, in particular tyrosine phosphorylation, is a revered hallmark of fertilization competency in our species, only a limited repository of phosphorylated substrates and kinases have ever been reported from human sperm. To broaden therapeutic targets for sperm targeted contraceptives and infertility therapies, we adapted a contemporary phosphoproteomic technique termed EasyPhos to generate bespoke methodology for the investigation of human sperm signalling. This approach yielded high depth phosphoproteomes of non-capacitated and capacitated human spermatozoa with in silico investigation of the phosphosites revealing 52 kinases with previously uncharacterized roles in sperm capacitation. Investigating the function of the putative sperm capacitation kinases identified yielded several kinases with novel roles in the regulation of sperm function. Of particular interest, polo like kinase 1 (PLK1) inhibition significantly reduced progressive sperm motility, attenuated capacitation-associated tyrosine phosphorylation and reduced the sperm acrosome reaction, an essential step to achieve fertilization. These findings reveal extensive phosphoproteome remodelling during human sperm capacitation, expanding the landscape of molecular targets for fertility control.

Cell Biology↗

bioRxiv2026

Structural Components for Calcitonin Gene-Related Peptide Signaling to Oligodendrocyte Precursor Cells

Oligodendrocyte precursor cells (OPCs) are unique glial cells that communicate bidirectionally with neurons. Neuronal inputs drive various OPC behaviors, including proliferation and differentiation, immunomodulation, blood brain barrier regulation, synapse engulfment and axonal remodeling. OPCs are implicated in numerous stress and pain conditions, where their involvement is likely driven by neuronal activity (ie. neurotransmitter and neuropeptide signaling). One neuropeptide causally involved in chronic pain and stress conditions is calcitonin gene-related peptide (CGRP). Here, we tested the hypothesis that OPCs receive direct inputs from CGRP-containing neurons in the adult brain. Using RNAscope, immunofluorescence and analysis of single-cell datasets, we find that OPCs express receptors for CGRP and we identify close spatial contacts between CGRP and OPCs, with nearly half of CGRP puncta occurring within 1 {micro}m of an OPC. Some of these contacts appear to be synaptic, with CGRP-OPC contacts colocalizing with the presynaptic protein Bassoon and the postsynaptic protein PSD-95. This work suggests the presence of both diffuse and more direct forms of CGRP signaling to OPCs, raising the importance of future experiments to identify both the mode of CGRP release onto OPCs and the functional effects of these different contact types.

neuroscience↗