Related Experiment Video

Updated: Dec 1, 2025

Author Spotlight: Investigating Islet Abnormalities and Function with a Pseudoislet Protocol
08:04

Author Spotlight: Investigating Islet Abnormalities and Function with a Pseudoislet Protocol

Published on: November 3, 2023

2.3K

CASK, APBA1, and STXBP1 collaborate during insulin secretion

Kai Zhang1, Tianyuan Wang1, Xingjing Liu1

  • 1Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, 210009, China.

Molecular and Cellular Endocrinology
|November 7, 2020
PubMed

Insights

Calcium/calmodulin-dependent serine protein kinase (CASK) is crucial for insulin secretion. This study reveals CASK forms a complex with APBA1 and STXBP1, essential for releasing insulin and potentially treating type 2 diabetes.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Molecular Biology

Background:

  • Insulin secretion is vital for glucose homeostasis.
  • Calcium/calmodulin-dependent serine protein kinase (CASK) is implicated in insulin vesicle trafficking.
  • Understanding CASK's role in insulin secretion is crucial for metabolic disease research.

Purpose of the Study:

  • To elucidate the molecular interactions of CASK during insulin secretion.
  • To investigate the tripartite complex involving CASK, APBA1, and STXBP1.
  • To explore the therapeutic potential of CASK in type 2 diabetes.

Main Methods:

  • Co-immunoprecipitation assays to identify protein interactions.
  • Liquid chromatography-mass spectrometry for protein identification.
  • Bioinformatic analysis to understand complex formation and function.

Main Results:

  • CASK, APBA1, and STXBP1 form a tripartite complex during insulin secretion.
  • CASK enhances APBA1-STXBP1 interaction and mediates their transport to the plasma membrane.
  • High fatty acid levels impair insulin secretion by reducing CASK, APBA1, and STXBP1 expression.
  • CASK overexpression can rescue lipotoxicity-induced insulin release defects.

Conclusions:

  • CASK plays a critical role in insulin granule exocytosis.
  • The CASK/APBA1/STXBP1 complex is a key regulator of insulin secretion.
  • CASK represents a potential therapeutic target for type 2 diabetes mellitus.
Keywords:
APBA1CASKInsulin secretionSTXBP1T2DM

More Related Videos

Coculture Analysis of Extracellular Protein Interactions Affecting Insulin Secretion by Pancreatic Beta Cells05:51

Coculture Analysis of Extracellular Protein Interactions Affecting Insulin Secretion by Pancreatic Beta Cells

Published on: June 15, 2013

13.3K
A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform09:35

A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform

Published on: July 16, 2016

11.5K

Related Concept Videos

Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

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...
6.2K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
1.9K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
15.2K
Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
916
Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
9.1K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
2.2K