Biology subjects

Nys, J.

Publications and source records attributed to Nys, J..

3 recordsLinked to original sources

bioRxiv2026

Extracellular neuroligin-ICAM5 coupling drives dendritic growth via actin remodeling

Neuroligins (NLGNs) organize neuronal connectivity by engaging a diverse set of interaction partners, yet how extracellular recognition couples to intracellular growth programs remains unclear. Using affinity proteomics, we identify intercellular adhesion molecule-5 (ICAM5), a cell-surface protein localized to dendritic filopodia, as a novel neuroligin interactor. Surface plasmon resonance and cell-based assays demonstrate direct binding between the ICAM5 and NLGN3 extracellular domains and reveal that ICAM5 engages all neuroligin isoforms. ICAM5 is required for NLGN-induced dendritic outgrowth, but the NLGN3-ICAM5 complex does not contribute to synaptogenesis. Mechanistically, ICAM5 sustains PAK-Cofilin signaling and F-actin organization in growth cones, positioning it as a downstream effector that links neuroligin engagement to actin remodeling. Together, these findings define a neuroligin-ICAM5 axis that couples extracellular recognition to intracellular actin remodeling to control neuronal structural development.

neuroscience↗

bioRxiv2025

FLASH or flare: variable intestinal toxicity results in a mouse model following proton pencil beam scanning irradiation on a clinical superconducting synchrocyclotron

Background and aimsUltra-high dose rate (FLASH) irradiation is a promising technique to reduce radiation-induced normal tissue toxicities while preserving antitumor efficacy. We evaluated the feasibility and intestinal sparing potential of FLASH irradiation using a clinical synchrocyclotron-based proton therapy system generating a pulsed beam. Material and methodsC57BL/6J mice received abdominal irradiation (2x2 cm) in transmission mode at FLASH (>60 Gy/s) or conventional (CONV, 0.5 Gy/s) dose rates using a 230 MeV superconducting synchrocyclotron proton pencil beam scanning (PBS) system. Two independent irradiation rounds were performed. Endpoints included 75-day survival, regenerating crypt counts, whole blood counts at day 4, and intestinal wall thickness, cyst-like structures, and cytokine levels at day 75. ResultsIn the first irradiation round, survival after 14.5 Gy FLASH was markedly improved (5/8 survivors) compared to CONV (0/8), whereas in the second round, survival rates were identical (2/7 per group). Overall, pooled data indicated improved survival with 14.5 Gy FLASH. The LD50 was 13.74 Gy in CONV and 14.48 Gy in FLASH mode, corresponding to a FLASH modifying factor of 0.95. FLASH at 14.5 Gy increased regenerating crypt numbers compared to CONV, but only in the first round, supporting survival outcomes. No significant differences were observed in whole blood counts, cytokine profiles, or long-term intestinal structural changes between groups. ConclusionFLASH proton therapy delivered with a clinical synchrocyclotron PBS system can reduce short-term gastrointestinal toxicity in mice. However, inconsistent results across irradiation rounds highlight limitations of this model for reliable FLASH studies.

cancer biology↗

bioRxiv2019

SorCS1-mediated Sorting of Neurexin in Dendrites Maintains Presynaptic Function

The pre- and postsynaptic membranes comprising the synaptic junction differ in protein composition. The mechanisms that maintain the polarized distribution of synaptic membrane proteins are poorly understood. The sorting receptor SorCS1 is a critical trafficking regulator of neuronal receptors, including neurexin (Nrxn), a presynaptic adhesion molecule essential for synaptic transmission. We find that SorCS1 controls a balance between axonal and dendritic Nrxn1 surface levels. Newly synthesized Nrxn1 traffics to the somatodendritic surface, followed by endocytosis. SorCS1 interacts with the Rab11 effector protein Rab11FIP5/Rip11 to facilitate the transition of internalized Nrxn1 from early to recycling endosomes and bias Nrxn1 surface polarization toward the axon. In the absence of SorCS1, Nrxn1 accumulates in early endosomes and mis-polarizes to the dendritic surface, impairing presynaptic function. The axonal/dendritic balance of Nrxn1 surface distribution is activity-dependent, indicating that SorCS1-mediated sorting in somatodendritic endosomes dynamically controls Nrxn1 axonal surface polarization required for proper presynaptic function.

neuroscience↗