Breaking News
April 26, 2019 - Can Obesity Shrink Your Brain?
April 26, 2019 - This oral appliance could help you (and your partner) sleep better
April 26, 2019 - Myelination deficits cause abnormal hypersocial behavior associated with Williams syndrome
April 26, 2019 - New sepsis detector uses photonics to make accurate diagnosis in less than thirty minutes
April 26, 2019 - New study describes process to diagnose rare genetic diseases in record time
April 26, 2019 - Scientists and patients gather in Vancouver to discuss about Stevens-Johnson syndrome
April 26, 2019 - Advance in breakthrough cancer treatment eliminates serious side effects
April 26, 2019 - Discovery about cold sensing could pave way for new pain relief drugs
April 26, 2019 - Children often turn to sugary drinks instead of water
April 26, 2019 - Genome analysis shows the combined effect of many genes on cognitive traits
April 26, 2019 - Patients Caught In Middle Of Fight Between Health Care Behemoths
April 26, 2019 - Drug overdoses among adolescents and young adults on the rise
April 26, 2019 - Implementing a Paperless QC Micro Laboratory”
April 25, 2019 - Obesity linked to a reduction in gray matter
April 25, 2019 - Smart assistants could help combat opioid crisis
April 25, 2019 - Diagnostic stewardship strategy reduces inappropriate testing
April 25, 2019 - Three-antibiotic cocktail eradicates ‘persister’ Lyme bacteria in mouse model
April 25, 2019 - Study investigates how early blindness shapes sound processing
April 25, 2019 - Outcomes Worse for Cancer Patients Seen at Noncancer EDs
April 25, 2019 - Link found between temperament of high-risk infants and obesity
April 25, 2019 - Al Letson explores ties between journalists and doctors at Medicine and the Muse symposium
April 25, 2019 - New mobile phone game can detect people at risk of Alzheimer’s
April 25, 2019 - Scientists discover trigger region for absence epileptic seizures
April 25, 2019 - Stretchy wearable patch can do a health check while you work out
April 25, 2019 - Exercise activates brain circuits associated with memory in older adults
April 25, 2019 - Veggies, Fruits and Grains Keep Your Heart Pumping
April 25, 2019 - Healthy meal kits can boost children’s long-term health
April 25, 2019 - Designing an inexpensive surgical headlight: A Q&A with a Stanford surgeon
April 25, 2019 - States Weigh Banning A Widely Used Pesticide Even Though EPA Won’t
April 25, 2019 - Integrator complex proteins are crucial for healthy brain development in fruit flies, study finds
April 25, 2019 - Device converts brain signals into speech, offering hope for patients
April 25, 2019 - Measles vaccination rates are a ‘public health time bomb’
April 25, 2019 - Maths made easier for scientists students who shun the subject wins award
April 25, 2019 - Researchers decode how cancer drug works in brains of Parkinson’s disease patients
April 25, 2019 - Smarter Brain Cancer Trial Comes to Columbia
April 25, 2019 - Researchers Seek Sage Advice Of Elders On Aging Issues
April 25, 2019 - New chemical synthesis strategy leads to identification of novel, simpler derivatives
April 25, 2019 - Vanderbilt investigators discover link between vascular biology and eye disease
April 25, 2019 - Feces transplantation is effective and provides economic benefits
April 25, 2019 - Eisenhower Health first in Southern California to offer new lung valve treatment for COPD/emphysema
April 25, 2019 - Johns Hopkins researchers uncover role of neurotransmitter in the spread of aggressive cancers
April 25, 2019 - Porvair Sciences offers highly effective P3 microplate for biological sample clean-up
April 25, 2019 - Air pollution increases risk for respiratory hospitalization among childhood cancer survivors
April 25, 2019 - We are sitting more! How bad is that?
April 25, 2019 - Majority of stroke survivors not screened for osteoporosis, despite increased risk
April 25, 2019 - ADHD Screening: MedlinePlus Lab Test Information
April 25, 2019 - Cellular alterations increase vulnerability of obese and diabetic individuals to infection
April 25, 2019 - Association Insurance Pushes On Despite Court Ruling
April 25, 2019 - Traditional and e-cigarette users may be more receptive to smoking cessation interventions
April 25, 2019 - Delving into tumor’s cellular lineage may offer clues for customized therapies
April 25, 2019 - Two studies uncover brain mechanisms underlying decision making process
April 25, 2019 - Cardiometabolic Risk Better ID’d in Children Reclassified to Higher BP
April 25, 2019 - How the obesity epidemic is taking a toll on our bones and joints
April 25, 2019 - E-cigarettes contaminated with dangerous microbial toxins
April 25, 2019 - Researchers document specific characteristics of storefront tobacco advertisements
April 25, 2019 - Oncotype DX-guided treatment could reduce cost for breast cancer care, study suggests
April 25, 2019 - Predicting whether a patient will benefit from chemotherapy
April 25, 2019 - New review highlights how lifestyle affects our genes
April 25, 2019 - Study provides evidence that blood tests can detect Alzheimer’s risk
April 25, 2019 - Computer program mimics natural speech using brain signals from epilepsy patients
April 25, 2019 - Physicians turning to antibiotic alternatives for long-term acne treatment
April 25, 2019 - Preschool Is Prime Time to Teach Healthy Lifestyle Habits
April 25, 2019 - Study finds insidious and persistent discrimination among physician mothers
April 25, 2019 - Newly identified skin-gut communication helps illuminate link between food allergy and eczema
April 25, 2019 - Thiazide use linked with reduced risk of low energy fractures in people with Alzheimer’s
April 25, 2019 - Some women are biologically more resilient than others to PTSD
April 25, 2019 - The Current issue of “The view from here” is concerned with Partnerships and Alliances
April 25, 2019 - Imaging method reveals long-lived patterns in cells of the eye
April 25, 2019 - Podcast: KHN’s ‘What The Health?’ The Abortion Wars Rage On
April 25, 2019 - Prolonged exposure therapy is more effective in treating veterans with PTSD, alcohol use disorder
April 24, 2019 - Our artificial cornea breakthrough could lead to self-assembling organs
April 24, 2019 - A Stanford black, female, gay surgery resident speaks out
April 24, 2019 - Donna Lynne on Extreme Sports, Lessons From the '60s, and Taking CUIMC to the Next Level
April 24, 2019 - Pain Clinics’ Doctors Needlessly Tested Hundreds Of Urine Samples, Court Records Show
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
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