Structure, interaction and nervous connectivity of beta cell primary cilia

Affiliations
  • 1Molecular Diabetology, University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany. andreas.mueller1@tu-dresden.de.
  • 2Paul Langerhans Institute Dresden (PLID) of Helmholtz Munich, University Hospital Carl Gustav Carus and Faculty of Medicine, TU Dresden, Dresden, Germany. andreas.mueller1@tu-dresden.de.
  • 3German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany. andreas.mueller1@tu-dresden.de.
  • 4Human Technopole (HT), Milan, Italy.
  • 5Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
  • 6Yale School of Medicine, New Haven, CT, USA.
  • 7Molecular Diabetology, University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • 8Paul Langerhans Institute Dresden (PLID) of Helmholtz Munich, University Hospital Carl Gustav Carus and Faculty of Medicine, TU Dresden, Dresden, Germany.
  • 9German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  • 10DFG Cluster of Excellence “Physics of Life”, TU Dresden, Dresden, Germany.
  • 11Department of Chemical Engineering, Cooper Union, New York City, NY, USA.
  • 12Center for Molecular and Cellular Bioengineering (CMCB), Technology Platform, Core Facility Electron Microscopy and Histology, TU Dresden, Dresden, Germany.
  • 13Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, TU Dresden, Dresden, Germany.
  • 14HELMHOLTZ IMAGING, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany.
  • 15Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA.
  • 16Human Technopole (HT), Milan, Italy. gaia.pigino@fht.org.
  • 17Molecular Diabetology, University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany. michele.solimena@tu-dresden.de.
  • 18Paul Langerhans Institute Dresden (PLID) of Helmholtz Munich, University Hospital Carl Gustav Carus and Faculty of Medicine, TU Dresden, Dresden, Germany. michele.solimena@tu-dresden.de.
  • 19German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany. michele.solimena@tu-dresden.de.
  • 20DFG Cluster of Excellence “Physics of Life”, TU Dresden, Dresden, Germany. michele.solimena@tu-dresden.de.

Published on:

Abstract

Primary cilia are sensory organelles present in many cell types, partaking in various signaling processes. Primary cilia of pancreatic beta cells play pivotal roles in paracrine signaling and their dysfunction is linked to diabetes. Yet, the structural basis for their functions is unclear. We present three-dimensional reconstructions of beta cell primary cilia by electron and expansion microscopy. These cilia are spatially confined within deep ciliary pockets or narrow spaces between cells, lack motility components and display an unstructured axoneme organization. Furthermore, we observe a plethora of beta cell cilia-cilia and cilia-cell interactions with other islet and non-islet cells. Most remarkably, we have identified and characterized axo-ciliary synapses between beta cell cilia and the cholinergic islet innervation. These findings highlight the beta cell cilia’s role in islet connectivity, pointing at their function in integrating islet intrinsic and extrinsic signals and contribute to understanding their significance in health and diabetes.

Related Concept Videos

JoVE Research Video for Microtubules in Signaling 01:22

1.6K

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary…

JoVE Research Video for Mechanism of Ciliary Motion 01:05

3.4K

The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are…

JoVE Research Video for Assembly of Complex Microtubule Structures 01:32

1.7K

Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.

JoVE Research Video for Hair Cells 01:22

38.3K

Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.

Hair cells are named…

JoVE Research Video for Microtubules in Cell Motility 01:24

2.9K

Microtubules are thick hollow cylindrical proteins that help form the cytoskeleton. Microtubules have varied roles in the cell. These filaments help form cellular appendages like cilia and flagella, which are responsible for locomotion. The cilia arise from basal bodies, separated from the main body by a membrane-like structure forming the transition zone. This zone is the gate for the entry of lipids and proteins, creating a unique composition of lipids and proteins in the ciliary membrane and…

JoVE Research Video for Insulin Secretory Vesicles 01:05

4.4K

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of…