Related Experiment Video
Updated: Jun 27, 2025
10:30
Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
Published on: October 15, 2014
20.6K
Interplay between myotubularins and Ca2+ homeostasis
Ning Dai1, Jody Groenendyk1, Marek Michalak1
1Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Summary
The myotubularin (MTM) family of phosphatases, including MTM1 and MTMRs, are crucial for cellular functions. This study reveals their significant impact on calcium (Ca2+) signaling pathways, vital for muscle and nerve health.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- The myotubularin (MTM) family comprises phosphatases with a conserved protein tyrosine phosphatase domain.
- Nine MTM family members possess an active C(X)5R phosphatase domain, dephosphorylating phosphoinositides like PtdIns(3)P.
- Mutations in MTM genes are linked to severe human disorders, including myopathies and neuropathies.
Purpose of the Study:
- To investigate the multifaceted roles of MTM1 and myotubularin-related proteins (MTMRs).
- To elucidate the influence of MTM1/MTMRs on calcium (Ca2+) signaling and homeostasis.
- To understand the contribution of MTM-dependent Ca2+ signaling to myopathies and neuropathies.
Main Methods:
- Bioinformatic analysis of MTM family members.
- Biochemical assays to determine phosphatase activity.
- Cellular studies examining Ca2+ signaling dynamics.
- Genetic analysis of MTM mutations in disease models.
Main Results:
- MTM1, MTMR6, and MTMR14 were identified as key regulators of Ca2+ signaling.
- Dysregulation of MTM-mediated phosphoinositide metabolism affects Ca2+ homeostasis.
- Altered Ca2+ signaling pathways are implicated in MTM-dependent neuromuscular disorders.
Conclusions:
- The myotubularin family plays a critical role beyond phosphoinositide dephosphorylation, significantly impacting Ca2+ signaling.
- Understanding MTM-dependent Ca2+ regulation offers new therapeutic avenues for myopathies and neuropathies.
- MTM1/MTMRs represent a crucial link between phosphoinositide metabolism and cellular Ca2+ dynamics.
Related Concept Videos
01:29Relaxation of Skeletal Muscles
3.2K
The period of muscle contraction primarily influences the duration of stimulation at the neuromuscular junction (NMJ), the presence of free calcium ions in the sarcoplasm, and the availability of energy or ATP to support contractions.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open....
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open....
3.2K
01:26Cross-bridge Cycle
117.4K
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
117.4K
01:27Feedback Regulation of Calcium Concentration
3.4K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.4K
01:16Actin and Myosin in Muscle Contraction
10.6K
Actin and myosin are contractile proteins that form the sarcomere found in skeletal muscle tissues for regulating muscle contraction. Actin, a globular contractile protein, interacts with myosin for muscle contraction. The skeletal tissue appears striped or striated under a microscope due to the repeated arrangement of contractile proteins actin and myosin along the length of myofibrils. Dark A bands and light I bands repeat along myofibrils, and the alignment of myofibrils in the cell causes...
10.6K
01:20Excitation-Contraction Coupling in Skeletal Muscles
8.2K
Excitation-contraction coupling is a series of events that occur between generating an action potential and initiating a muscle contraction. It occurs at the triad, a structure found in skeletal muscle fibers that comprise a T-tubule and terminal cisternae of the sarcoplasmic reticulum on each side. These triads are visible in longitudinally sectioned muscle fibers. They are typically located at the A-I junction — the junction between the A and I bands of the sarcomere.
When an action...
When an action...
8.2K
01:16Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K