Primary cilia coordinate c-KIT signaling induced proliferation in alpha cells
- 1Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Denmark
Abstract
Circulating glucagon levels are elevated in patients with diabetes and obesity and contribute to hyperglycemia. The mechanisms underlying hyperglucagonemia remain poorly understood, but expansion of pancreatic -cell mass is thought to play an important role. Primary cilia are sensory organelles that act as signaling hubs, for pathways controlling cell differentiation, proliferation, and function, yet their contribution to -cell biology remains poorly defined. Here we investigated the role of primary cilia in the regulation of -cell proliferation. To this end we generated the first -cell primary cilia proteome identifying 167 cilia-enriched proteins. Among these, we identified and validated the proto-oncogene receptor tyrosine kinase, c-KIT, as a novel ciliary receptor in -cells. We further show that c-KIT signaling depends on intact primary cilia and that stimulation of isolated mouse islets with its endogenous ligand, stem cell factor (SCF), promotes -cell proliferation. In human pancreatic islets KITLG mRNA expression, but not KIT mRNA expression, correlated positively with donor BMI, suggesting that increased ligand availability drives c-KIT signaling in obesity. Together, our findings identify the primary cilium as a signaling platform c-KIT in cells and reveal a ciliary axis that may drive -cell expansion and hyperglucagonemia in obesity and diabetes.
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BibTeX
@misc{deshar2026primary,
title = {{Primary cilia coordinate c-KIT signaling induced proliferation in alpha cells}},
author = {G. Deshar and M. G. Aslanyan and G. D. Diwan and A. Karagiannopoulos and T. Beyer and F. Campestre and A. Vilas and I. Cozar-Castellano and L. Eliasson and R. B. Russell and K. Boldt and R. Roepman and S. T. Christensen and L. B. Pedersen and J. G. Knudsen},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750659},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750659v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Primary cilia coordinate c-KIT signaling induced proliferation in alpha cells
AU - G. Deshar
AU - M. G. Aslanyan
AU - G. D. Diwan
AU - A. Karagiannopoulos
AU - T. Beyer
AU - F. Campestre
AU - A. Vilas
AU - I. Cozar-Castellano
AU - L. Eliasson
AU - R. B. Russell
AU - K. Boldt
AU - R. Roepman
AU - S. T. Christensen
AU - L. B. Pedersen
AU - J. G. Knudsen
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750659
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750659v1
AB - Circulating glucagon levels are elevated in patients with diabetes and obesity and contribute to hyperglycemia. The mechanisms underlying hyperglucagonemia remain poorly understood, but expansion of pancreatic -cell mass is thought to play an important role. Primary cilia are sensory organelles that act as signaling hubs, for pathways controlling cell differentiation, proliferation, and function, yet their contribution to -cell biology remains poorly defined. Here we investigated the role of primary cilia in the regulation of -cell proliferation. To this end we generated the first -cell primary cilia proteome identifying 167 cilia-enriched proteins. Among these, we identified and validated the proto-oncogene receptor tyrosine kinase, c-KIT, as a novel ciliary receptor in -cells. We further show that c-KIT signaling depends on intact primary cilia and that stimulation of isolated mouse islets with its endogenous ligand, stem cell factor (SCF), promotes -cell proliferation. In human pancreatic islets KITLG mRNA expression, but not KIT mRNA expression, correlated positively with donor BMI, suggesting that increased ligand availability drives c-KIT signaling in obesity. Together, our findings identify the primary cilium as a signaling platform c-KIT in cells and reveal a ciliary axis that may drive -cell expansion and hyperglucagonemia in obesity and diabetes.
ER -