Breaking News
January 22, 2019 - Amgen And UCB Receive Positive Vote From FDA Advisory Committee In Favor Of Approval For Evenity (romosozumab)
January 22, 2019 - Does being bilingual make children more focused? Study says no
January 22, 2019 - Study reveals new genes and biological pathways linked to osteoarthritis
January 22, 2019 - FSU study provides better understanding of spinal cord injuries
January 22, 2019 - Delaying bath for newborn babies increases breastfeeding rates, finds study
January 21, 2019 - Many parents still try non-evidence-based cold prevention methods for children
January 21, 2019 - High Levels of Activity, Motor Ability Linked to Better Cognition
January 21, 2019 - Killer blows? Knockout study of pair of mouse MicroRNA provides cancer insight
January 21, 2019 - Buffalo researchers receive grant to quicken development of generic equivalents of contraceptives
January 21, 2019 - One-third of pregnant women do not believe cannabis is harmful to their fetus
January 21, 2019 - Fiderstat could be used as chemopreventative drug for intestinal cancers caused by APC gene mutations
January 21, 2019 - Modifying healthcare delivery practices may improve discussions between youth and healthcare providers
January 21, 2019 - UNIST researcher named as recipient of Merck’s 2018 Life Science Awards
January 21, 2019 - How Getting a Flu Shot Could Save Your Life
January 21, 2019 - Surgical adhesions can be treated, prevented in mice
January 21, 2019 - Increased physician-targeted marketing associated with higher opioid overdose deaths
January 21, 2019 - Researchers uncover specific microbial signatures of intestinal disease
January 21, 2019 - Simple blood test reliably detects signs of Alzheimer’s damage before symptoms
January 21, 2019 - Study to investigate new targeted oral treatments for severe asthma
January 21, 2019 - Plan Your Plate | NIH News in Health
January 21, 2019 - Fecal occult blood test may improve CRC outcomes in some
January 21, 2019 - Blood test detects Alzheimer’s disease years before symptoms develop
January 21, 2019 - Mount Sinai joins with Paradigm and ReqMed to repurpose drug for treatment of MPS
January 21, 2019 - FDA Advisory Committee Votes on Zynquista (sotagliflozin) as Treatment for Adults with Type 1 Diabetes
January 21, 2019 - The causes and complications of snoring
January 21, 2019 - Placenta adapts and compensates when pregnant mothers have poor diets or low oxygen
January 21, 2019 - New implant could restore the transmission of electrical signals in injured central nervous system
January 21, 2019 - Rapid-acting fentanyl test strips found to be effective at reducing overdose risk
January 21, 2019 - Coronary Artery Calcium May Help Predict CVD in South Asians
January 21, 2019 - The mystery of the super-ager
January 21, 2019 - Scientists develop smart microrobots that can change shape depending on their surroundings
January 21, 2019 - Keep Moving to Keep Brain Sharp in Old Age
January 21, 2019 - Despite progress, gay fathers and their children still structurally stigmatized
January 21, 2019 - New drug for treating liver parasites in vivax malaria
January 21, 2019 - Merck recognized with 2018 Life Science Industry Award for best use of social media
January 21, 2019 - Coeur Wallis equips the canton of Valais with 260 SCHILLER defibrillators
January 21, 2019 - Scientists propose quick and pain-free method for diagnosing kidney cancer
January 21, 2019 - Signs of memory loss could point to hearing issues
January 21, 2019 - HeartFlow Analysis shows highest diagnostic performance for detecting coronary artery disease
January 21, 2019 - How Much Caffeine is Too Much?
January 21, 2019 - Take a timeout before you force your child to apologize
January 21, 2019 - Scientists design two AI algorithms to improve early detection of cognitive impairment
January 21, 2019 - Novel therapy for children with chronic hormone deficiency provides lifeline for parents
January 21, 2019 - Bioethicists call for oversight of poorly regulated, consumer-grade neurotechnology products
January 21, 2019 - Study shows hereditary hemochromatosis behind many cancers and joint diseases
January 21, 2019 - Short bouts of stairclimbing throughout the day can improve cardiovascular health
January 20, 2019 - Liver Transplant Survival May Improve With Race Matching
January 20, 2019 - Study implicates hyperactive immune system in aging brain disorders
January 20, 2019 - Cancer Diagnosis May Quadruple Suicide Risk
January 20, 2019 - Parkinson’s disease experts devise a roadmap
January 20, 2019 - Research brings new hope to treating degenerative brain diseases
January 20, 2019 - Scientists pinpoint a set of molecules that wire the body weight center of the brain
January 20, 2019 - Researchers get close to developing elusive blood test for Alzheimer’s disease
January 20, 2019 - UCLA researchers demonstrate new technique to develop cancer-fighting T cells
January 20, 2019 - Researchers discover how cancer cells avoid genetic meltdown
January 20, 2019 - Exercise makes even the ‘still overweight’ healthier: study
January 20, 2019 - University of Utah to establish first-of-its-kind dark sky studies minor in the US
January 20, 2019 - School-based nutritional programs reduce student obesity
January 20, 2019 - Improved maternity care practices in the southern U.S. reduce racial inequities in breastfeeding
January 20, 2019 - New enzyme biomarker test indicates diseases and bacterial contamination
January 20, 2019 - Republican and Democratic governors have different visions to transform health care, say researchers
January 20, 2019 - Researchers discover that spin flips happen in only half a picosecond in the course of a chemical reaction
January 20, 2019 - Suicide Risk Up More Than Fourfold for Cancer Patients
January 20, 2019 - Doctors find 122 nails in Ethiopian’s stomach
January 20, 2019 - UV disinfection technology eliminates up to 97.7% of pathogens in operating rooms
January 20, 2019 - Researchers discover mechanism which drives leukemia cell growth
January 20, 2019 - AHA: Infection as a Baby Led to Heart Valve Surgery for Teen
January 20, 2019 - Injection improves vision in a form of childhood blindness
January 20, 2019 - Multiple sclerosis therapies delay progression of disability
January 20, 2019 - New study finds infrequent helmet use among bike share riders
January 20, 2019 - Clearing up information about corneal dystrophies
January 20, 2019 - Researchers describe new behavior in energy metabolism that refutes existing evidence
January 20, 2019 - New study takes first step toward treating endometriosis
January 20, 2019 - Researchers find how GREB1 gene promotes resistance to prostate cancer treatments
January 20, 2019 - Replacing Sitting Time With Activity Lowers Mortality Risk
January 20, 2019 - A simple, inexpensive intervention makes birth safer for moms and babies in parts of Africa
January 19, 2019 - New anti-inflammatory compound acts as ‘surge protector’ to reduce cancer growth
January 19, 2019 - Significant flaws found in recently released forensic software
January 19, 2019 - New Leash on Life? Staying Slim Keeps Pooches Happy, Healthy
January 19, 2019 - Men and women remember pain differently
Scientists find fast way to manipulate cell’s cilia

Scientists find fast way to manipulate cell’s cilia

image_pdfDownload PDFimage_print

Scientists at Johns Hopkins Medicine and the National Tsing Hua University in Taiwan say they have found a fast way to manipulate a cell’s cilia, the tiny, fingerlike protrusions that “feel” and sense their microscopic environment. The experiments, performed in mouse cells, may advance scientists’ efforts to not only understand how the nanosized antennae work, but also how to repair them.

A report of their findings appeared online April 30 in Nature Communications.

With few exceptions, most cells in the body have cilia or can grow them. The tiny antenna sense chemicals such as hormones and growth factors, which regulate cell health and growth. Cilia also detect mechanical and physical cues in the body, such as light, gravity, sound and the flow of blood and urine.

When cilia malfunction, a range of human diseases and conditions can occur. For example, problems with cilia in kidney cells can cause polycystic kidney disease, an incurable condition in which fluid-filled cysts interfere with kidney function and which is conventionally treated with dialysis.

Because cilia are so small — 10,000 times smaller than a cell — scientists have long found it challenging to squeeze their tools into such tight spaces to study them.

“When I was a postdoc, a colleague in a neighboring laboratory was studying cilia, and I hoped that by combining his knowledge of the biology of cilia with my expertise in cellular engineering, we could figure out how to manipulate cilia within their tiny spaces,” says Takanari Inoue, Ph.D., professor of cell biology at the Johns Hopkins University School of Medicine and an author of the new report.

After years of work, he says they figured out a way to manipulate a chemical signaling pathway within cilia that controls how molecules are shuttled up and down the length of the tiny structure.

To do it, Inoue and his colleagues in Taiwan used a tool called chemically inducible dimerization, which they say is faster than efforts to manipulate the pathway by rewriting the cilia’s genetic code. The tool, essentially, is a matchmaker — it helps to mesh two specific chemicals together at specific sites within a living cell.

For the new study, Inoue and his colleagues added a protein called FRB to cells from mice grown in the laboratory. The FRB protein is capable of glomming onto a rigid structure within cilia, called a microtubule, which acts as a railway, shuttling proteins up and down the length of cilia.

Then they added a molecule called FKBP to the cells, which is attached to an enzyme that acts as an eraser for a chemical modification in the cilia called glutamylation. The FKBP and enzyme pair floats around the cell until scientists add a chemical called rapamycin, which causes FKBP to get trapped at FRB molecules within the cilia.

Once inside the cilia, the enzyme attached to the FKBP molecule selectively erases the glutamylation modification inside the cilia. It also ignores other signaling pathways.

The scientists call their molecule matchmaking STRIP, for spatiotemporal rewriting intraciliary post-translational modifications.

As a result of rapidly removing glutamylation in cilia, the scientists found that molecules flowed up the cilia, toward the tip, more slowly — about .3 micrometers per second — compared with .4 micrometers per second, using a dead enzyme that doesn’t affect glutamylation.

“We think our technique is faster than existing means of tracking cilia activity and enables scientists to access cilia parts faster and dive into specific chemical modifications for certain amounts of time,” says Inoue.

“Our STRIP system offers a new strategy for precisely controlling microtubule modifications in living cells. With this approach, it becomes possible to understand how microtubules regulate cellular functions and may also serve as a new way to treat human diseases in the future,” says Yu-Chun Lin, Ph.D., an assistant professor at the Institute of Molecular Medicine at the National Tsing Hua University in Taiwan.

Other diseases affected by flawed cilia include a brain disorder called Joubert syndrome, a kidney disorder called nephronophthisis, retinitis pigmentosa and a rare disorder called situs inversus, in which the internal organs of the body are in the reverse location of their normal position.

The scientists also found that microtubules in the mouse cells that are not located inside cilia were not affected when they tinkered with glutamylation.

Inoue and his colleagues also found that the genetic output of a developmental pathway called Hedgehog (which is connected to glutamylation) is decreased in cells treated with STRIP compared with their controls.

Inoue and his colleagues say they now plan to apply STRIP to human cells and look more closely at the molecular process of glutamylation in cilia. They may also use STRIP to control other chemical modifications within cilia.

Source:

https://www.hopkinsmedicine.org/news/media/releases/scientists_develop_method_to_tweak_tiny_antenna_on_cells

Tagged with:

About author

Related Articles