Dataset Information

Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing.

ABSTRACT: Hyperglycemia increases glucose concentrations in the cerebrospinal fluid (CSF), activating glucose-sensing mechanisms and feeding behavior in the hypothalamus. Here, we discuss how hyperglycemia temporarily modifies ependymal cell ciliary beating to increase hypothalamic glucose sensing. A high level of glucose in the rat CSF stimulates glucose transporter 2 (GLUT2)-positive subcommissural organ (SCO) cells to release SCO-spondin into the dorsal third ventricle. Genetic inactivation of mice GLUT2 decreases hyperglycemia-induced SCO-spondin secretion. In addition, SCO cells secrete Wnt5a-positive vesicles; thus, Wnt5a and SCO-spondin are found at the apex of dorsal ependymal cilia to regulate ciliary beating. Frizzled-2 and ROR2 receptors, as well as specific proteoglycans, such as glypican/testican (essential for the interaction of Wnt5a with its receptors) and Cx43 coupling, were also analyzed in ependymal cells. Finally, we propose that the SCO-spondin/Wnt5a/Frizzled-2/Cx43 axis in ependymal cells regulates ciliary beating, a cyclic and adaptive signaling mechanism to control glucose sensing.

SUBMITTER: Nualart F

PROVIDER: S-EPMC10513282 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing.

Nualart Francisco F Cifuentes Manuel M Ramírez Eder E Martínez Fernando F Barahona María José MJ Ferrada Luciano L Saldivia Natalia N Bongarzone Ernesto R ER Thorens Bernard B Salazar Katterine K

PLoS biology 20230921 9

Hyperglycemia increases glucose concentrations in the cerebrospinal fluid (CSF), activating glucose-sensing mechanisms and feeding behavior in the hypothalamus. Here, we discuss how hyperglycemia temporarily modifies ependymal cell ciliary beating to increase hypothalamic glucose sensing. A high level of glucose in the rat CSF stimulates glucose transporter 2 (GLUT2)-positive subcommissural organ (SCO) cells to release SCO-spondin into the dorsal third ventricle. Genetic inactivation of mice GLU ...[more]

PMID: 37733692

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Project description:Cerebrospinal fluid is a clear fluid that occupies the ventricular and subarachnoid spaces within and around the brain and spinal cord. Cerebrospinal fluid is a dynamic signaling milieu that transports nutrients, waste materials and neuroactive substances that are crucial for the development, homeostasis and functionality of the central nervous system. The mechanisms that enable cerebrospinal fluid to simultaneously exert these homeostatic/dynamic functions are not fully understood. SCO-spondin is a large glycoprotein secreted since the early stages of development into the cerebrospinal fluid. Its domain architecture resembles a combination of a matricellular protein and the ligand-binding region of LDL receptor family. The matricellular proteins are a group of extracellular proteins with the capacity to interact with different molecules, such as growth factors, cytokines and cellular receptors; enabling the integration of information to modulate various physiological and pathological processes. In the same way, the LDL receptor family interacts with many ligands, including β-amyloid peptide and different growth factors. The domains similarity suggests that SCO-spondin is a matricellular protein enabled to bind, modulate, and transport different cerebrospinal fluid molecules. SCO-spondin can be found soluble or polymerized into a dynamic threadlike structure called the Reissner fiber, which extends from the diencephalon to the caudal tip of the spinal cord. Reissner fiber continuously moves caudally as new SCO-spondin molecules are added at the cephalic end and are disaggregated at the caudal end. This movement, like a conveyor belt, allows the transport of the bound molecules, thereby increasing their lifespan and action radius. The binding of SCO-spondin to some relevant molecules has already been reported; however, in this review we suggest more than 30 possible binding partners, including peptide β-amyloid and several growth factors. This new perspective characterizes SCO-spondin as a regulator of cerebrospinal fluid activity, explaining its high evolutionary conservation, its apparent multifunctionality, and the lethality or severe malformations, such as hydrocephalus and curved body axis, of knockout embryos. Understanding the regulation and identifying binding partners of SCO-spondin are crucial for better comprehension of cerebrospinal fluid physiology.

Dataset Information

Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing.

Publications

Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing.

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