Breaking News
February 23, 2019 - Hepatocellular carcinoma diagnosis, prognosis and treatment may improve by identifying a protein
February 23, 2019 - The American Heart Association issues new reference toolkit for healthcare providers
February 23, 2019 - Studies explore physiological dangers that climate change will have on animal life
February 23, 2019 - Penn study reveals increase in health-related internet searches before ER visits
February 23, 2019 - Intensive therapy during early stages of MS leads to better long-term outcomes
February 23, 2019 - Prenatal Fluconazole Exposure Increases Neonatal Risks
February 23, 2019 - Mental Health Screening: MedlinePlus Lab Test Information
February 23, 2019 - Study suggests birth mechanics are part of the process that leads to autism
February 23, 2019 - Unhealthy diet linked to poor mental health
February 23, 2019 - Study gives a snapshot of crocodile evolution
February 23, 2019 - Research finds steep rise in self-poisonings among young people
February 23, 2019 - American Gastroenterological Association announces “AGA Future Leaders Program”
February 23, 2019 - Scientists uncover new mechanisms regulating neural stem cells
February 23, 2019 - Combinations of certain insecticides turn out to be lethal for honeybees
February 23, 2019 - AHA News: Why Are Black Women at Higher Risk of Dying From Pregnancy Complications?
February 23, 2019 - NIMH » Anxiety Disorders
February 23, 2019 - Autistic people urgently need access to tailored mental health support
February 23, 2019 - Newly designed molecule could benefit people with Friedrich’s Ataxia
February 23, 2019 - Chinese CRISPR twins may have better cognition and memory
February 23, 2019 - Study finds new genetic clues associated with asthma in African ancestry populations
February 23, 2019 - Fetal signaling pathways may offer future opportunities to treat lung damage
February 23, 2019 - Early-stage osteoarthritis drug wins prestigious innovation award
February 23, 2019 - Researchers report positive findings with dasotraline for ADHD in children ages 6-12
February 23, 2019 - News study reanalyzes the effects of noncaloric sweeteners on gut microbiota
February 23, 2019 - New device allows scientists to reproduce blow effects on the heart in lab
February 23, 2019 - Holy herb identified as a potential treatment for Alzheimer’s disease
February 23, 2019 - New technology platform digitally counts growth factors in single cells
February 23, 2019 - Surgery and other treatments offer viable options for adult scoliosis
February 23, 2019 - Reduced antibody adaptability may make the elderly more vulnerable to influenza
February 23, 2019 - Researchers find increased rates of CRC screening in Kentucky after Medicaid expansion
February 23, 2019 - Neighborhood income, education associated with risk of disability progression in MS patients
February 23, 2019 - Endocrine Society opposes new rule that restricts access to Title X Family Planning Program
February 23, 2019 - 2019 guidelines for management of patients with atrial fibrillation
February 23, 2019 - Surprise rheumatoid arthritis discovery points to new treatment for joint inflammation
February 23, 2019 - A just-right fix for a tiny heart
February 23, 2019 - UMass Amherst scientist explores role of citrus peel in decreasing gut inflammation
February 23, 2019 - Owlstone Medical and Shanghai Renji Hospital collaborate to initiate breath biopsy lung cancer trial
February 23, 2019 - AMSBIO’s comprehensive portfolio of knock-out cell lines and lysates
February 23, 2019 - New app reliably determines physicians’ skills in forming accurate, efficient diagnoses
February 23, 2019 - Peripheral nerve injury can trigger the onset and spread of ALS, shows study
February 23, 2019 - Researchers uncover mechanisms that prevent tooth replacement in mice
February 23, 2019 - Once-a-day capsule offers new way to reduce symptoms of chronic breathlessness
February 23, 2019 - FDA Adds Boxed Warning for Increased Risk of Death with Gout Medicine Uloric (febuxostat)
February 23, 2019 - Phone-based intervention aids rheumatoid arthritis care
February 23, 2019 - Opioid epidemic makes eastern inroads and targets African-Americans
February 23, 2019 - New identified biomarker predicts patients who might benefit from HER2-targeted agents
February 23, 2019 - Study offers new insights into mechanisms of changes in erythrocytes under stress
February 23, 2019 - Antipsychotic polypharmacy may be beneficial for schizophrenia patients
February 23, 2019 - Researchers investigate how marijuana and tobacco co-use affects quit attempts by smokers
February 23, 2019 - Patients with diabetes mellitus have high risk of stable ischemic heart disease
February 23, 2019 - Transparency on healthcare prices played key role in Arizona health system’s turnaround
February 23, 2019 - A comprehensive, multinational review of peppers around the world
February 23, 2019 - Study finds modest decrease in burnout among physicians
February 23, 2019 - A simple change can drastically reduce unnecessary tests for urinary tract infections
February 23, 2019 - Deep Learning-Enhanced Device Detects Diabetic Retinopathy
February 23, 2019 - Researchers discover new binding partner for amyloid precursor protein
February 23, 2019 - Modest decrease seen in burnout among physicians, researchers say | News Center
February 23, 2019 - Transplanting bone marrow of young mice into old mice prevents cognitive decline
February 23, 2019 - Mogrify to accelerate novel IP and cell therapies using $3.7m USD funding
February 23, 2019 - Johns Hopkins study describes cells that may help speed bone repair
February 23, 2019 - Scientists demonstrate influence of food odors on proteostasis
February 23, 2019 - Researchers unlock the secret behind reproduction of fish called ‘Mary’
February 23, 2019 - Acupuncture Could Help Ease Menopausal Symptoms
February 23, 2019 - Researchers use AI to detect early signs of Alzheimer’s
February 23, 2019 - On recovery, vulnerability and ritual: An exhibit in white | News Center
February 23, 2019 - Memory Stored in Unexpected Region of the Brain
February 23, 2019 - Several health experts worldwide gather at EUDONORGAN event
February 23, 2019 - Discovery of potent compound in native California shrub may lead to treatment for Alzheimer’s
February 22, 2019 - Researchers create new map of the brain’s own immune system
February 22, 2019 - ICHE’s reviews on surgical infections, unnecessary urine tests, and nurses’ role in antibiotic stewardship
February 22, 2019 - UK Research and Innovation invests £200 million to create new generation of AI leaders
February 22, 2019 - Takeda collaboration to boost fight against Alzheimer’s and other neurodegenerative diseases
February 22, 2019 - Heavy drinking may change DNA, leading to increased craving for alcohol
February 22, 2019 - U.S. opioid deaths jump fourfold in 20 years; epidemic shifts to Eastern states | News Center
February 22, 2019 - 5 Questions with William Turner on Diversity in Medicine
February 22, 2019 - HHS Finalizes Rule Seeking To Expel Planned Parenthood From Family Planning Program
February 22, 2019 - Researchers uncover biochemical pathway that may help identify drugs to treat Alzheimer’s
February 22, 2019 - Biologist uses new grant to find ways to eliminate schistosomiasis
February 22, 2019 - Bag-mask ventilation to help patients breathe during intubation prevents complications
February 22, 2019 - AbbVie Announces New Drug Application Accepted for Priority Review by FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis
Study reveals how mTORC1-driven changes in crowding could influence major diseases

Study reveals how mTORC1-driven changes in crowding could influence major diseases

image_pdfDownload PDFimage_print

Among the most studied protein machines in history, mTORC1 has long been known to sense whether a cell has enough energy to build the proteins it needs to multiply as part of growth. Because faulty versions of mTORC1 contribute to the abnormal growth seen in cancer, drugs targeting the complex have been the subject of 1,300 clinical trials since 1970.

Now a new study finds that mTORC1 has a second function of profound importance: controlling how “crowded” human cells become.

Led by researchers at NYU School of Medicine and published online in the journal Cell on June 21, the finding explains for the first time the workings of a physical quality that cells use to regulate their actions, and more closely links malfunctions in mTORC1-related genes to several diseases of aging.

“Our results begin to clarify how mTORC1-driven changes in crowding could cause the insides of human cells to solidify as a person ages, packing more proteins into the same space and interfering with functions that require them to move around,” says senior study author Liam Holt, PhD, assistant professor in the Institute for Systems Genetics at NYU Langone Health. “This work may also help explain the origin of the solid protein clumps that appear in the cells of patients with cardiovascular diseases, diabetes and Alzheimer’s.”

Freedom to Move

Based on past studies, biologists have long concluded that cells require for survival a limit on the number of proteins in their fluid-filled inner spaces, the cytoplasm where many cellular functions occur.

Specifically, the current study found that the mTORC1 complex controls crowding by determining the number of ribosomes, multi-protein machines that build other proteins there.

By engineering cells to make their own glowing tracers to measure crowding, the researchers showed that, by adjusting levels of mTORC1 action, they could cause a two-fold swing in the ability of multi-protein cellular machines to move around (diffuse) in the cytoplasm of human kidney cells.

Experiments further confirmed ribosomes as the main “crowding agent” regulated by mTORC1, influencing the physical environment of large molecules – like those particularly important to cell growth and death – but leaving alone reactions depending on single proteins.

Many proteins are barely dissolved in the cell, with as much chance of glomming onto each other as to interact with the liquid surrounding them. Crowding increases the chances that these like-structured molecules will together undergo a shift from one state of matter to another (e.g. liquid to a solid), say the authors. In one such “phase transition,” similar proteins spread out in the cytoplasmic fluid come together to form dense liquid droplets, the way oil forms its own globs in vinegar.

“The biological consequences of phase changes are an area of intense inquiry right now, with emerging theories suggesting that genetic material, for instance, forms droplets that help to turn genes on and off,” says Holt, also faculty in the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health.

By separating protein complexes into phase-separated droplets, or into even denser gels, the cell forms semi-compartments that do not mix as freely with their surroundings, spaces in which more distinct, faster biological reactions can proceed.

The current study suggests that malfunctioning mTORC1 may increase crowding, and therefore cause droplets and gels to become the solids found in cells with diseases of aging – like the tau fibers that build up in the brain tissue of Alzheimer’s patients.

Furthermore, the decades of limited success by mTORC1-based cancer drugs could proceed in part from the crowding effect, says Holt. For example, mTORC1 activation may be important to initiate cancer in some cases, but could hinder aggressive growth later as cancer cells become crowded with ribosomes. Thus, the current line of work may help to set new guidelines about when to use mTORC1 inhibitors based on the stage of a patient’s cancer.

Moving forward, the team also is studying how crowding affects phase change in different cell types, with the long-term goal of designing anti-crowding therapies for neurodegeneration and cancer.

Source:

https://nyulangone.org/press-releases/crowding-inside-cells-influences-many-functions-major-diseases

Tagged with:

About author

Related Articles