Breaking News
December 14, 2018 - New discovery will improve the safety and predictability of CRISPR
December 14, 2018 - Geneticists discover how sex-linked disorders arise
December 14, 2018 - New method to visualize small-molecule interactions inside cells
December 14, 2018 - Study describes mechanism that makes people more vulnerable to hunger-causing stimuli
December 14, 2018 - Chronic opioid therapy associated with increased healthcare spending and hospital stays
December 14, 2018 - Blood Types
December 14, 2018 - Obesity linked to increased risk of early-onset colorectal cancer
December 14, 2018 - Blood test helps identify distinct molecular signatures in children with cystic fibrosis
December 14, 2018 - Scientists use water to track electrical activity of nerve cells
December 14, 2018 - Recurrence of urinary tract infection may depend on bacterial strain, study shows
December 14, 2018 - GBT Announces U.S. FDA Agrees with its Proposal Relating to Accelerated Approval Pathway for Voxelotor for the Treatment of Sickle Cell Disease and GBT Plans to Submit New Drug Application (NDA)
December 14, 2018 - Partial Thromboplastin Time (PTT) Test: MedlinePlus Lab Test Information
December 14, 2018 - Common tactics for health promotion at work may be detrimental to employees with obesity
December 14, 2018 - Myths about migration and health not supported by available evidence
December 14, 2018 - Recent findings on rare genetic disorder may help develop new treatment options
December 14, 2018 - New drug shows promise in treating sarcomas
December 14, 2018 - Scientists perform lung lavage as new approach for tuberculosis diagnosis in rhinoceros
December 14, 2018 - Recent winners of the Nobel Medicine Prize
December 14, 2018 - KHN’s ‘What the Health?’ Insurance enrollment is lagging — and there are lots of reasons why
December 14, 2018 - Study assesses safety and efficacy of new treatment for pancreatic cancer
December 14, 2018 - Study finds drug targets for Ebola, Dengue, and Zika viruses
December 14, 2018 - Study highlights need for personalized approach to treat ICU acquired delirium
December 14, 2018 - Soot particles from road traffic significantly contribute to air pollution
December 14, 2018 - Massage helps relieve pain, improve mobility in patients with knee osteoarthritis
December 14, 2018 - Researchers explore home healthcare nurses’ knowledge attitudes toward infection control
December 14, 2018 - Average outpatient visit in the U.S. costs nearly $500, shows new study
December 14, 2018 - Reference Infliximab, Biosimilar Equivalent for Crohn’s Disease
December 14, 2018 - New contact lens to treat eye injuries
December 14, 2018 - Acne could have a genetic basis find researchers promising new cure
December 14, 2018 - Higher physical activity associated with improved mood
December 14, 2018 - New UGA study points to optimal hypertension treatment for stroke patients
December 14, 2018 - Study highlights factors that can reduce food cravings
December 14, 2018 - Researchers discover Ebola-fighting protein in human cells
December 14, 2018 - Fentanyl surpasses heroin in cause of U.S. drug overdose deaths
December 14, 2018 - When Heart Attack Strikes, Women Often Hesitate to Call for Help
December 14, 2018 - A warning about costume contacts
December 14, 2018 - Study examines link between peripheral artery disease and heart attack
December 14, 2018 - Researchers develop biotechnological tool to produce antifungal proteins in plants
December 14, 2018 - 3D-printed adaptive aids can benefit patients with arthritis
December 14, 2018 - Chronic bullying during adolescence impacts mental health
December 14, 2018 - Integral Molecular and Merus collaborate to develop bispecific antibody therapeutics
December 13, 2018 - Importance of cell cycle and cellular senescence in the placenta discovered
December 13, 2018 - Gold “nanoprisms” open new window into vessels and single cells
December 13, 2018 - Research findings could lead to new targets for cancer-fighting therapeutics
December 13, 2018 - Butantan Institute signs collaboration agreement with MSD to develop dengue vaccines
December 13, 2018 - Study explores how patients want to discuss symptoms with doctors
December 13, 2018 - RUDN medics first to gather scattered data on hepatitis morbidity in Somalia
December 13, 2018 - Age and gender disparities found in use of bed nets to prevent malaria in sub-Saharan Africa
December 13, 2018 - Caffeine therapy benefits developing brains of premature babies
December 13, 2018 - New review focuses on electrospinning techniques used in musculoskeletal tissue engineering
December 13, 2018 - A new division focused on human immune system
December 13, 2018 - Zogenix Announces Positive Phase 3 Trial Results on the Efficacy and Safety of Fintepla (ZX008) in Dravet Syndrome
December 13, 2018 - BCR ABL Genetic Test: MedlinePlus Lab Test Information
December 13, 2018 - Caffeinated beverages during pregnancy linked to lower birth weight babies
December 13, 2018 - Stanford Medicine Health Trends Report examines opportunity to democratize health care
December 13, 2018 - Obsessive-compulsive disorder may protect individuals from obesity
December 13, 2018 - Scientists investigate how a painful event is processed in the brain
December 13, 2018 - Genetic study reveals new insights into underlying causes of moderate-to-severe asthma
December 13, 2018 - Study uncovers new genetic clues to frontotemporal dementia
December 13, 2018 - Vitamin C supplementation for pregnant smokers may reduce harm to infants’ lungs
December 13, 2018 - New study reveals yin-yang personality of dopamine
December 13, 2018 - Research identifies nerve-signaling pathway behind sustained pain after injury
December 13, 2018 - Children with high levels of callous traits show widespread differences in brain structure
December 13, 2018 - Long-term Benefit of Steroid Injections for Knee Osteoarthritis Challenged
December 13, 2018 - Adding new channels to the brain remote control
December 13, 2018 - In the Spotlight: A different side of neuroscience
December 13, 2018 - Medical Marvels: Using immunotherapy for melanoma that spread to the brain
December 13, 2018 - Puzzles do not keep dementia away finds study
December 13, 2018 - New mouse model shows potential for rapid identification of promising muscular dystrophy therapies
December 13, 2018 - Study reveals urban and rural differences in prenatal exposure to essential and toxic elements
December 13, 2018 - New collaborative partnership in quest of novel antibiotics
December 13, 2018 - Single tau molecule holds clues to help diagnose neurodegeneration in its earliest stages
December 13, 2018 - AHA Scientific Statement: Low Risk of Side Effects for Statins
December 13, 2018 - What Is Acute Flaccid Myelitis?
December 13, 2018 - How bereaved people control their thoughts without knowing it
December 13, 2018 - Health care democratization underway, according to 2nd annual Stanford Medicine Health Trends Report | News Center
December 13, 2018 - Going Beyond a Single Color
December 13, 2018 - London-based startup launches ‘thedrug.store’ aiming to clean up CBD industry
December 13, 2018 - Loss of tight junction barrier protein results in gastric cancer development
December 13, 2018 - Novel way to efficiently deliver anti-parasitic medicines
New discovery may offer insight into treating sickle cell anemia and other blood disorders

New discovery may offer insight into treating sickle cell anemia and other blood disorders

image_pdfDownload PDFimage_print

Discovery by Scripps Research scientists may offer insight into treating blood disorders such as sickle cell anemia.

Red blood cells are on a wild ride. As they race through the body to deliver oxygen, they must maintain a distinct dimpled shape—and bounce back into form even after squishing through narrow capillaries. Red blood cells that can’t keep their shape are associated with diseases like sickle cell anemia.

In a new study, Velia Fowler, PhD, and her lab at The Scripps Research Institute report that a protein called myosin IIA contracts to give red blood cells their distinctive shape. The findings, published this week in the journal Proceedings of the National Academy of Sciences, could shed light on sickle cell diseases and other disorders where red blood cells are deformed.

“Red blood cells have been studied for centuries, but there are still a lot of unanswered questions about how they adopt their shape,” says Alyson Smith, graduate student at Scripps Research and co-first author of the study. “Our study adds an important piece to this puzzle.”

Red blood cells look like puffy disks with concave “dimples” on top and bottom. But the blood cells of people with certain disorders take on other shapes. In severe forms of sickle cell diseases, genetic disorders most common among people of African descent, the cells are shaped like crescent moons or sickles.

These misshapen cells are rigid and sticky, causing them to become stuck in blood vessels, which prevent the blood from carrying oxygen throughout the body, causing anemia. About 300,000 children are born with sickle cell anemia each year, and there is currently no cure for these disorders.

Scientists have long wondered how healthy red blood cells maintain their dimpled shape, and whether it is a passive or active process. Are they just like rubber inner tubes that passively bounce back to their former shape after being squeezed or bumped? Or is something mechanical in the cell membrane—the outer skin of the cell—actively contracting and relaxing to maintain the shape? Answering these questions could also help explain what goes wrong when red blood cells are too rigid to deform easily as they flow through blood vessels.

Smith and Roberta Nowak, a research assistant, led the work to solve this puzzle, which had piqued Fowler’s interest since she was a postdoctoral researcher in the 1980s. They found that red blood cells actively regulate their shape, thanks to myosin IIA—which is related to the protein that drives muscle contraction in other parts of the body.

The team used advanced microscopes at Scripps Research to capture 3D images showing myosin IIA under the cell membrane. The researchers found that red blood cell myosin IIA molecules assemble into barbell-shaped structures called filaments. Specialized regions at both ends of the myosin IIA filaments can pull on a membrane-associated structural protein called actin to control the stiffness of the cell membrane.

“You need active contraction on the cell membrane, similar to how muscles contract,” says Fowler. “The myosin pulls on the actin to provide tension in the membrane, and then that tension maintains the biconcave shape.”

The team then treated red blood cells with a compound called blebbistatin, which stops myosin from working properly. They found that the treated cells lost their ability to maintain a shape and looked floppy and unhealthy. This further confirmed that myosin IIA is important for maintain red blood cell shape.

Understanding the architecture of the membrane is an important step toward finding the causes of diseases where red blood cells are deformed. Fowler says there might be a chance someday to inhibit myosin IIA in red blood cells and restore some of elasticity they lose in sickle cell anemia, letting them bend and fit through capillaries.

“Even just a small change in those sickle cells might be enough,” says Nowak, who served as study co-first author with Smith.

This view of red blood cell shape has sparked many new questions. The study suggests that cells use a process called phosphorylation to make the myosin IIA filaments on the cell membrane more stable—but how this process is controlled remains a mystery. Going forward, the researchers hope to learn more about what regulates myosin IIA’s activity in red blood cells and even other cell types, like neurons.

Source:

https://www.scripps.edu/news/press/2018/20180404_blood_genetics.html

Tagged with:

About author

Related Articles