Breaking News
June 23, 2018 - FDA Alert: Kratom (mitragyna speciosa) powder products by Gaia Ethnobotanical: Recall
June 23, 2018 - CDC chief asks for, and gets, cut to his record $375K pay
June 22, 2018 - Novel cellular pathway may clarify how arterial inflammation develops into atherosclerosis
June 22, 2018 - Rutgers Cancer Institute educates childhood cancer survivors about late effects of treatment
June 22, 2018 - Study tests accuracy of device designed to detect heart dysfunction in childhood cancer survivors
June 22, 2018 - Study links annual haze with increased hospitalizations for respiratory problems
June 22, 2018 - Robotic surgery appears to be as effective as open surgery in treating bladder cancer
June 22, 2018 - Many Drugs Made Available Via FDA Expanded Access Programs
June 22, 2018 - Normal eye dominance is not necessary for restoring visual acuity in amblyopia
June 22, 2018 - Parent-Child Interaction Therapy can reduce depression rates in children
June 22, 2018 - Study provides insights into how components of different cells in the brain are altered
June 22, 2018 - Research does not confirm antidiabetic action of natural fatty acid derivatives
June 22, 2018 - Oxidative stress can be used against tumors to treat cancer
June 22, 2018 - Simple, cost-effective test may help improve early diagnosis of mild cognitive impairment
June 22, 2018 - New guide published to help battle fatal disease caused by kissing bugs
June 22, 2018 - Stigma Adds to Burden of Type 1 Diabetes
June 22, 2018 - In retinoblastoma survivors, oculo-visual issues tied to QoL
June 22, 2018 - Most adults with allergies do not use prescribed epinephrine even in emergency situations
June 22, 2018 - Study provides clues to how cancer cells develop resistance to chemotherapies
June 22, 2018 - New consensus paper serves as basis for uniform medical management of DSD
June 22, 2018 - Researchers work to identify areas of the brain that help us wake up
June 22, 2018 - Alcohol hangovers more significant and costly than people realize, shows research
June 22, 2018 - Targeting cells involved in blood vessel formation could hinder brain tumor growth
June 22, 2018 - Young cancer survivors need more support as they feel dissatisfied with their sexuality
June 22, 2018 - Unusual cell-to-cell communication in glioblastoma promotes aggressiveness and therapy resistance
June 22, 2018 - Turning A Phage – Drug Discovery Today
June 22, 2018 - World-first study links birth interventions and long-term childhood illness
June 22, 2018 - Improving the quality of biomedical research samples
June 22, 2018 - Researchers identify cerebral palsy using AI and DNA sequencing
June 22, 2018 - Administering nitric oxide gas after heart surgery may decrease risk of kidney problems
June 22, 2018 - Measuring levels of ethyl sulphate in hair can help assess alcohol consumption
June 22, 2018 - Researchers develop robot bloodhound that can rapidly detect odors on the ground
June 22, 2018 - AAA doses first patients in two clinical studies with PSMA-R2 for prostate cancer
June 22, 2018 - Researchers discover drug compound that inhibits movement of cancer cells
June 22, 2018 - Normalization of ‘plus-size’ body shapes may prevent recognition of health risks of obesity
June 22, 2018 - UC San Diego launches new bacteriophage therapy center
June 22, 2018 - New review outlines current state of sex-sensitive issues linked to heart failure drugs
June 22, 2018 - Pelvic pain a major issue for women nearing mid-life, research reveals
June 22, 2018 - Researchers develop reliable DNA barcodes for biomedical research
June 22, 2018 - New risk-prediction model may help identify diabetic patients at high risk of pancreatic cancer
June 22, 2018 - Study reveals how mTORC1-driven changes in crowding could influence major diseases
June 22, 2018 - Researchers uncover new therapeutic opportunity in the treatment of malignant melanoma
June 22, 2018 - UC Riverside researcher receives grants to advance cancer, ALS research
June 22, 2018 - Radiation therapy alone may be enough to treat older, sicker patients with anal cancers
June 22, 2018 - Technical report describes how to make accurate particle size measurements on carbon black samples
June 22, 2018 - Nocdurna (desmopressin acetate) Approved by FDA as First Sublingual Tablet to Treat Nocturia due to Nocturnal Polyuria
June 22, 2018 - Neuroscientists locate neurons in the brain that respond when a visual target is found
June 22, 2018 - First human Keystone virus infection reported
June 22, 2018 - New study reveals how ‘good’ bacteria help in regulating our metabolism
June 22, 2018 - Osteopathic manual therapy affecting the diaphragm improves chronic low back pain
June 22, 2018 - Researchers create revolutionary model to study pulmonary diseases
June 22, 2018 - Diagnosing Heart Disease Using AI
June 22, 2018 - Increasing biodefense risks posed by synthetic biology
June 22, 2018 - Many Women Report Vasomotor Symptoms in Their 60s
June 22, 2018 - Rare mutation of gene carried by Quebec family gives insight into how the brain is wired
June 22, 2018 - Chemists find new way to make enzymes do a non-natural reaction
June 22, 2018 - Summer is good time to check for signs of skin cancer
June 22, 2018 - Innovative method can help identify patients with spastic cerebral palsy
June 22, 2018 - Exercise alters characteristics of blood to reduce inflammation in obese people
June 22, 2018 - Researchers examine complications across different types of breast reconstructive surgeries
June 22, 2018 - Rhesus macaque model could be useful to test therapies for congenital Zika virus syndrome
June 22, 2018 - AHA: New Insights Into Sickle Cell and Stroke Risk
June 22, 2018 - Doctors prescribe opioids at high rates to those at increased overdose risk
June 22, 2018 - Reduction in US cigarette smoking rates
June 22, 2018 - Preconception binge drinking may have negative effect on future offspring
June 22, 2018 - FDA expands approval of novel diabetes management device to include younger pediatric patients
June 22, 2018 - Researchers confirm weight loss benefits of the 16:8 diet
June 22, 2018 - FDA approves Eversense CGM system for use in adults with diabetes
June 22, 2018 - State opioid monitoring programs are not created equal
June 22, 2018 - Autistic teens who are bullied have higher rates of depression
June 22, 2018 - Penn Medicine team launches universal stroke awareness program
June 22, 2018 - Scientists discover the molecular trigger of necroptosis
June 22, 2018 - Researchers report unusually high levels of herpesvirus in the brains of people with Alzheimer’s disease
June 22, 2018 - Theoretical models predict how juveniles evolve to be more susceptible than adults to infection
June 22, 2018 - USC study reveals how the cell launches emergency response to repair damaged DNA
June 22, 2018 - $1.9 million grant aims to enhance behavioral health services in community-based settings
June 22, 2018 - New 3D imaging technique could improve arthritis treatment
June 22, 2018 - Cytokinetics Announces Data From Phase 2 Clinical Study of Reldesemtiv in Patients With Spinal Muscular Atrophy
June 22, 2018 - Polarized cells give the heart its fully developed form
June 21, 2018 - Stem cells appear to help fight obesity in animal models
Scientists visualize insulin receptor activation for the first time

Scientists visualize insulin receptor activation for the first time

image_pdfDownload PDFimage_print

As we are approaching the 100th anniversary of the discovery of insulin, a wide array of its signaling pathways has been defined. However, the initial step in insulin action, i.e. the engagement with its cell-surface receptor and the resulting conformational change, which propagates across the plasma membrane to the intracellular module, remains poorly understood. Addressing this problem, researchers from the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Hospital Carl Gustav Carus of TU Dresden together with colleagues from Rockefeller University New York succeeded for the first time in the visualization of the insulin receptor activation. The results of this collaborative work have now been published in the ‘Journal of Cell Biology’.

© Gutmann et al. 2018

Insulin exerts multiple effects on cellular metabolism and growth. The biological actions of insulin are mediated by a cell-surface receptor, called insulin receptor, which is present on the surface, i.e. the plasma membrane, of virtually all mammalian cells. The dysfunction of insulin receptor has been linked to severe pathologies including diabetes mellitus or cancer. Insulin binds outside the cell to the extracellular domain of its receptor and induces a structural change that is propagated across the membrane to the intracellular kinase domains inside the cell, causing them to activate each other, thus initiating signaling cascades. The nature of this structural change remained a mystery for decades, resulting in mutually exclusive models for insulin receptor activation being put forward.

“To obtain insights into receptor activation, we purified full-length insulin receptors and embedded them into nanodiscs, which are, as their name suggests, nanoscale disc-shaped membrane patches. Those could then be directly visualized by single-particle electron microscopy,” explains Theresia Gutmann, PhD student and co-first author of the study. She works at the Institute for Pancreatic Islet Research/Paul Langerhans Institute Dresden (IPI/PLID) which is run by Helmholtz Zentrum München together with the University Hospital Carl Gustav Carus of Technical University Dresden.

“This technology enables us to directly study the cell-surface receptors in an artificial membrane environment”, explains Dr. Ünal Coskun, group leader at IPI/PLID and co-senior author of the study. “In the absence of insulin, the receptor displays an inverted U-shaped ectodomain, which is consistent with previous crystallographic studies of isolated ectodomains, implying that the membrane-passing transmembrane domains and thus kinase domains are held well apart from each other.” “Upon insulin binding, the ectodomain of the receptor undergoes a dramatic reorganization, changing from a U-shaped to a T-shaped structure and also causing a rearrangement of the transmembrane domains. These now come together likely facilitating kinase domain interactions and thus their activation”, Dr. Thomas Walz, professor at the Rockefeller University, continues.

Dr. Coskun summarizes:

These nanodisc-embedded receptors provide a novel platform to address further questions regarding insulin receptor regulation and eventually to test therapeutic agents.

“Our results directly demonstrate the structural transition in the full-length receptor upon insulin binding and offer an answer to the longstanding question concerning the mechanism by which insulin activates its receptor, thus improving our understanding of the receptor,” concludes Gutmann. The authors from Dresden are scientists in the German Center for Diabetes Research (DZD).

Source:

https://www.helmholtz-muenchen.de/en/news/latest-news/press-information-news/article/44140/index.html

Tagged with:

About author

Related Articles