Biology subjects

Zahed Mohajerani, S.

Publications and source records attributed to Zahed Mohajerani, S..

2 recordsLinked to original sources

bioRxiv2026

Microfluidic analysis reveals ROCK2 regulation of endothelial cilia is essential for blood vessel lumen formation and vascular integrity

BackgroundThe formation of a patent vascular lumen is fundamental to circulatory function, a process governed by cytoskeletal dynamics and mechanosensory signalling. Endothelial cilia are present during blood vessel lumen development, but their precise functional role remains poorly understood. Understanding how cilia coordinate with endothelial cytoskeletal and signalling pathways is critical for elucidating mechanisms of vascular morphogenesis. MethodsWe have established a microfluidic system that recapitulates endothelial tube formation under fluid flow, enabling pharmacological and genetic manipulation with real-time visualisation of tube behaviour. Cilia, cytoskeletal dynamics, and lumen development were analysed in vitro, and in vivo. ResultsEarly perfusion in the microfluidic system induced a hierarchical vascular network. Inhibiting Rho-kinase (ROCK) or knocking down ciliary components (IFT88 and RPGRIPL1) suppressed lumen formation. ROCK inhibition or genetic ablation disrupted cilia in endothelial and non-endothelial cells, associated with LIM-kinase inhibition. Crucially, ROCK2 genetic ablation caused endothelial cilia loss, misorientation, and abrogated lumen formation, leading to haemorrhages and compromised vascular integrity in vivo. ConclusionsOur findings unveil a previously unrecognised co-regulation between cilia and ROCK signalling essential in vascular lumen formation.

cell biology↗

bioRxiv2024

Affinity purification mass spectrometry characterization of the interactome of receptor tyrosine kinase proline rich motifs in cancer

Receptor tyrosine kinase (RTK) overexpression is linked to the development and progression of multiple cancers. RTKs are classically considered to initiate cytoplasmic signalling pathways via ligand-induced tyrosine phosphorylation, however recent evidence points to a second tier of signalling contingent on interactions mediated by the proline-rich motif (PRM) regions of non-activated RTKs. The presence of PRMs on the C-termini of >40% of all RTKs and the abundance of PRM-binding proteins encoded by the human genome suggests that there is likely to be a large number of previously unexplored interactions which add to the RTK intracellular interactome. Here, we explore the RTK PRM interactome and its potential significance using affinity purification mass spectrometry and in silico enrichment analyses. Peptides comprising PRM-containing C-terminal tail regions of EGFR, FGFR2 and HER2 were used as bait to affinity purify bound proteins from different cancer cell line lysates. 490 unique interactors were identified, amongst which proteins with metabolic, homeostatic and migratory functions were overrepresented. This suggests that PRMs from RTKs may sustain a diverse interactome in cancer cells. Since RTK overexpression is common in cancer RTK PRM-derived signalling may be an important, but as yet underexplored, contributor to negative cancer outcomes including resistance to kinase inhibitors.

cell biology↗