CAMSAP2 localizes to the Golgi in islet β-cells and facilitates Golgi-ER trafficking

Area of Science:

• Cell Biology
• Endocrinology
• Molecular Biology

Background:

• Glucose stimulation triggers microtubule remodeling, enhancing insulin secretion in pancreatic beta cells.
• CAMSAP2 is known to stabilize microtubules by binding to their minus ends in cultured cells.

Purpose of the Study:

• To investigate the role of CAMSAP2 in primary pancreatic beta cells, particularly its function in glucose-stimulated insulin secretion (GSIS).
• To determine the localization and mechanism of CAMSAP2 action in primary beta cells.

Main Methods:

• Knockdown of CAMSAP2 in primary beta cells.
• Assessment of insulin content, insulin vesicle releasability, and GSIS.
• Immunofluorescence microscopy to determine CAMSAP2 localization.
• Analysis of Golgi-ER trafficking.

Main Results:

• CAMSAP2 knockdown reduced insulin content and attenuated GSIS in primary beta cells, without affecting insulin vesicle releasability.
• Contrary to expectations, CAMSAP2 knockdown did not alter microtubule stability.
• CAMSAP2 predominantly localized to the Golgi apparatus in primary beta cells, not microtubule minus ends, and this localization was independent of microtubule binding.
• CAMSAP2 knockdown impaired efficient Golgi-ER trafficking in primary beta cells.
• Evidence suggests primary beta cells and insulinoma cells express different CAMSAP2 isoforms.

Conclusions:

• A novel CAMSAP2 isoform in primary beta cells functions non-canonically to promote Golgi-ER trafficking.
• This CAMSAP2 isoform supports efficient insulin production and secretion, playing a key role in beta cell function.
• The findings reveal a new mechanism regulating insulin secretion beyond microtubule stabilization.