Breaking News
September 19, 2018 - Researchers develop more accurate measure of body fat
September 19, 2018 - Doctors and students rally to support gun violence research, education
September 19, 2018 - LEO Pharma and MorphoSys announce expansion of strategic alliance to develop peptide-derived drugs
September 19, 2018 - Seniors in pain hop aboard the canna-bus
September 19, 2018 - New compound could prevent malaria parasites from maturing inside mosquito
September 19, 2018 - Scientists find alterations in blood flow in response to body position change
September 19, 2018 - UNC Health Care extends free access to virtual care service in the aftermath of Hurricane Florence
September 19, 2018 - Opioid Refills Rare After Rhinoplasty
September 19, 2018 - Corn, obesity, and navigating healthy eating choices as a parent
September 19, 2018 - Journal editor aims to prompt thoughtful review of ethics in precision health
September 19, 2018 - Researchers identify key step in how plant cells respond to pathogens
September 18, 2018 - Researchers analyze how exposure to silver nanoparticles affects zebrafish
September 18, 2018 - Study shows air pollution may be bad for the fetus
September 18, 2018 - Coffee May Have Another Perk for Kidney Patients
September 18, 2018 - Tongue-in-cheek Nobels honor nutritional analysis of cannibalism, roller-coaster kidney stones treatment
September 18, 2018 - Progress, priorities, challenges are focus of State of Stanford Medicine | News Center
September 18, 2018 - Established Alzheimer’s Risk Gene Has a New Role
September 18, 2018 - Hospitalization after antibiotic initiation found to be higher for people with Alzheimer’s disease
September 18, 2018 - Many children with special healthcare needs do not have access to ‘PCMH-concordant’ care
September 18, 2018 - Investigational nasal influenza vaccine tested in children and teens
September 18, 2018 - Lymphatic vessels surrounding the brain play crucial role in multiple sclerosis, research suggests
September 18, 2018 - New fiber laser-based ultrasound sensor may have potential applications in medical diagnostics
September 18, 2018 - Protect your heart and health during ‘dog days’ of summer
September 18, 2018 - Faculty receive awards for promise in biomedical research, clinical care | News Center
September 18, 2018 - Digital games for CVD-related self-management improve exercise capacity and energy expenditure
September 18, 2018 - Aluminum inclusions help enhance adsorption of chemo drugs onto active carbon delivery capsule
September 18, 2018 - Adding PET scans to CT imaging can change treatment for women with cervical cancer
September 18, 2018 - UCSF awarded $20 million grant to study impacts of new, emerging tobacco products
September 18, 2018 - Human brains may be wired to prefer lying on the couch, suggests research
September 18, 2018 - Zika virus vaccine shows promise for treatment of fatal glioblastoma
September 18, 2018 - Theravance Biopharma and Mylan to Report New Data from Phase 3 Studies of Yupelri (revefenacin) in Oral Presentation at European Respiratory Society International Congress 2018
September 18, 2018 - INSiGHT identifies unique retinal regulatory genes
September 18, 2018 - Diversity, science leadership grants awarded to student-faculty pairs | News Center
September 18, 2018 - Many parents blame electronics for sleep problems among teens
September 18, 2018 - Researchers study neuronal activity in brain that prevents individuals from doing physical activity
September 18, 2018 - Purifying Proteins from Mammalian Cell Culture
September 18, 2018 - Researchers map 3D structure of toxic proteins used by Pseudomonas aeruginosa to trigger infection
September 18, 2018 - Outcome of ACL reconstruction related to the way you move post-surgery
September 18, 2018 - Study aims to investigate risk factors for PPCs in surgical patients with gastric cancer
September 18, 2018 - Ardelyx Submits New Drug Application for Tenapanor for IBS-C
September 18, 2018 - Sociodemographic disparities in eyeglass use among elderly
September 18, 2018 - New Drug Shows Promise for Progressive Form of MS
September 18, 2018 - Babies exposed to higher levels of organochlorine compounds in womb may have worse lung function
September 18, 2018 - Women exposed to trauma in their lives gave birth to underweight male infants
September 18, 2018 - Probiotic supplementation may reduce use of antibiotics, scientific analysis shows
September 18, 2018 - Resveratrol decreases pain severity and levels of inflammatory biomarkers in osteoarthritis patients
September 18, 2018 - Research shows pollution is reaching the placenta
September 18, 2018 - KAIST researchers develop heart-targeting drug delivery technology using tannin acid
September 18, 2018 - Muscle relaxants used during general anesthesia can increase risk of pulmonary complications
September 18, 2018 - Silicone breast implants may increase risk of rare adverse outcomes in women
September 18, 2018 - Pediatricians Have a Role in Encouraging Play Among Children
September 18, 2018 - California’s Medicaid program hits ‘print’ when the feds need info
September 18, 2018 - Genes, environment and schizophrenia—new study finds the placenta is the missing link
September 18, 2018 - Boehringer Ingelheim announces study results of COPD patients treated with Spiolto Respimat
September 18, 2018 - PAREXEL launches Patient Innovation Center to improve drug development process
September 18, 2018 - Children’s National and NIAID launch pediatric clinical research partnership
September 18, 2018 - Researchers may be overlooking complexities in social relations of primates
September 18, 2018 - Key signaling molecule that helps stem cells make healthy bone declines as we age
September 18, 2018 - More women veterans with chronic pain use CIH therapies than men
September 18, 2018 - As Earth Warms, Heat-Related Deaths Will Multiply
September 18, 2018 - Labetalol use up for patients with preeclampsia and asthma
September 18, 2018 - MoreGrasp project shows significant results in field of thought-controlled grasp neuroprosthetics
September 18, 2018 - Drumming can benefit school children with autism
September 18, 2018 - Busyness can help people to make virtuous choices, research shows
September 18, 2018 - Two-minute bursts of in-class exercise breaks do not disrupt learning and teaching
September 18, 2018 - New online tools aid surgeons and specialists who care for older people
September 18, 2018 - Researchers use CRISPR to identify gene that helps cells resist flavivirus infection
September 18, 2018 - Brain’s support cells may play a central role in repetitive behaviors related to OCD
September 18, 2018 - Scientists discover novel mechanism by which synthesized proteins reach target compartment in cell
September 18, 2018 - Easy and rapid test for viral infections can cut antibiotic use, hospitalizations
September 18, 2018 - Gunshot victims more likely to require blood transfusions and die than other trauma patients
September 18, 2018 - Cyclacel Pharmaceuticals Announces Initiation of Phase 1b/2 Clinical Trial of Sapacitabine With Olaparib in BRCA Mutant Breast Cancer
September 18, 2018 - Older adults fitted with cochlear implants exhibit poor brain function
September 18, 2018 - Inexpensive testing spurs cancer patients’ relatives to assess own disease risk | News Center
September 18, 2018 - Aging may have originated at the very beginning of life, says study
September 18, 2018 - New research on sperm quality updates advice for couples trying to conceive
September 18, 2018 - Paracetamol use in infancy may increase risk of developing asthma by the age of 18
September 18, 2018 - Promising gene therapy for ‘day blind’ sheep now safe for clinical trials in human patients
September 18, 2018 - New research shows evidence of soot from polluted air in placentas
September 17, 2018 - Expanding primary care buprenorphine treatment could curb opioid overdose crisis
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