Connect with us

BIOLOGY

For the first time, scientists ‘see’ dual-layered scaffolding of cellular nuclei

Charles Roper

Published

on

Our cells sometimes have to squeeze through pretty tight spaces. And when they do, the nuclei inside must go along for the ride. Using super-sensitive microscopic imaging, a team of scientists from the University of Pittsburgh and Carnegie Mellon University have made a fundamental biological discovery that explains the structure of the nuclear envelope and gives tantalizing clues as to how cells squish through narrow openings without springing a leak.

The findings, which also could be key to untangling the mechanisms underlying several genetic diseases, are described today in the Proceedings of the National Academy of Sciences.

“It’s quite the serendipitous discovery,” said Quasar Padiath, M.B.B.S., Ph.D., associate professor in the Pitt Graduate School of Public Health’s Department of Human Genetics and one of the senior authors on the research. “Just like everyone else, I thought we knew how the cellular nuclear envelope was organized, but as we took a closer look while investigating a genetic condition, we found that there was far more to the story.”

Every animal cell contains a nucleus, home to the majority of its genetic material. Lining the interior of the membrane encasing the nucleus is the nuclear lamina, a scaffold that gives the nucleus its spherical structure. Scientists had previously shown the lamina to be formed by a tangled meshwork of filaments, made up of proteins called lamin A and B.

Padiath teamed up with Yang Liu, Ph.D., associate professor in Pitt’s departments of medicine and bioengineering, to take a closer look at the nuclear lamina because people with a fatal genetic condition he studies—autosomal dominant leukodystrophy with autonomic disease (ADLD) – have extra copies of the gene that codes for lamin B1, a subtype of lamin B. The scientists first looked at the lamina in normal cells using a super-resolution imaging technique called “stochastic optical reconstruction microscopy” (STORM).

To their surprise, the team discovered that there are actually two distinct meshworks—an outer, more loosely woven layer of lamin B and an inner, tighter layer of lamin A.

Using super-sensitive microscopic imaging, a team of scientists made a fundamental biological discovery that explains the structure of the nuclear envelope and gives tantalizing clues as to how cells squish through narrow openings without springing a leak. Credit: UPMC

“It is truly remarkable that STORM is able to visualize such a microscopically small separation between lamin A and B1,” said Liu, who also is a researcher at the UPMC Hillman Cancer Center. “That has never been seen with conventional light microscopy.”

Padiath’s team then built on an ongoing partnership with Kris Dahl, Ph.D., a Carnegie Mellon University professor of chemical engineering who studies the mechanics and architecture of nuclear membranes, to learn about how the lamin layers function. By imaging nuclei under varying degrees of pressure, the scientists discovered that when a cell is compressed, the outer, more loosely woven lamin B1 layer thins, allowing the lamin A layer to bulge out at the axes of the nucleus.

“For me, this process is similar to one of my knitting projects,” said Dahl. “Based on the holes between the stitches and the thickness of the yarn, you can predict the stiffness of the material.”

The scientists believe their observations indicate that the distinct lamin layers are part of a necessary cellular system: When functioning correctly, it allows nuclei to relieve pressure when compressed by biologic functions—such as moving within a very thin blood vessel or squeezing through a narrow opening—to avoid damage to the nucleus itself.

In the disease that Padiath studies—ADLD—patients typically live into their 40s and 50s before experiencing symptoms tied to fatal brain degradation. Because ADLD involves extra copies of the lamin B1 gene, Padiath’s future work will explore how excessive lamin B could negatively impact brain cells at middle age.

“Now that we can look at the nuclear architecture in such exquisite detail, we can start asking, ‘How does it change in ADLD and other lamina diseases, particularly with aging?'” Padiath said.


Explore further:
Organizing a cell’s genetic material from the sidelines

More information:
Bruce Nmezi el al., “Concentric model predicts distinct roles for the A and B type lamins in the spatial organization and stability of the nuclear lamina,” PNAS (2019). www.pnas.org/cgi/doi/10.1073/pnas.1810070116

Journal reference:
Proceedings of the National Academy of Sciences

Provided by:
University of Pittsburgh

Co-host on the H.P.S.N. talk show and co-founder of the Human Parasites Support Network. Content contributor, survivor and victim of a parasitic infection. #Computer guy. #WebDeveloper #Marketer #Entrepreneur #BusinessOwner #UniversityofOklahoma

Continue Reading
Advertisement
Click to comment

Leave a Reply

Your email address will not be published. Required fields are marked *

Medical News

MEDICAL10 hours ago

Quick Take: Association of Systemic Antibiotic Treatment of Acne With Skin Microbiota Characteristics

Systemic antibiotics are commonly used in the treatment of acne. However, the impact of their use on the complete bacterial...

MEDICAL10 hours ago

New herpes zoster vaccine predicted to be more cost effective than predecessor  

1. In a computational model, the new “recombinant zoster vaccine” (RZV) was predicted to be most cost-effective than the previous...

MEDICAL22 hours ago

Chinese population study shows high prevalence of elevated cardiovascular disease risk and low utilization of pharmacotherapy

1. In this national screening project, around 10% of middle-aged Chinese subjects were found to be at “high risk” for...

MEDICAL1 day ago

The KATHERINE trial: trastuzumab emtansine more effective than trastuzumab alone for treating residual HER2-positive breast cancer

1. Patients with residual human epidermal growth factor receptor 2 (HER2)-positive breast cancer after chemotherapy and HER2 targeted therapy had...

MEDICAL2 days ago

Peripheral perfusion-targeted resuscitation does not lower mortality in septic shock patients

1. In this randomized controlled trial, there was no difference in 28-day mortality in patients with early septic shock between...

MEDICAL2 days ago

The CLEAR trial: decolonization routine associated with lower infection risk among MRSA carrier patients

1. Hospitalized patients with known MRSA colonization randomized to undergo a decolonization routine were found to have lower risks of...

MEDICAL3 days ago

Addition of IV acetaminophen with propofol or dexmedetomidine reduces risk of post-operative delirium in older patients undergoing cardiac surgery

1. In this randomized controlled trial, post-operative scheduled intravenous (IV) acetaminophen combined with propofol or dexmedetomidine reduced risk of post-operative...

MEDICAL3 days ago

Nurse-led psychological intervention does not reduce PTSD symptoms in ICU patients

1. In this randomized clinical trial, nurse-led psychological interventions did not reduce PTSD risk at 6 months compared to care...

MEDICAL4 days ago

2-Question Screen Identifies Adolescents at Risk for Future Alcohol Use Disorders

1. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) 2-question screen showed high predictive validity in identifying adolescents at...

MEDICAL4 days ago

MYBPC3 haploinsufficiency results in hypertrophic cardiomyopathy by altering myosin head configurations [PreClinical]

1. Truncating mutations in cardiac myosin-binding protein C (MYBPC3) are a common genetic cause of hypertrophic cardiomyopathy. 2. Haploinsufficiency of...

Advertisement

#CDC

Do you have questions about preventing and managing high #cholesterol? Join @CDCHeart_Stroke and a panel of cholesterol experts for a Facebook Live event on February 25 at 12:30 pm ET. Tune in at facebook.com/millionhearts. #HeartMonth

test Twitter Media - Do you have questions about preventing and managing high #cholesterol? Join @CDCHeart_Stroke and a panel of cholesterol experts for a Facebook Live event on February 25 at 12:30 pm ET. Tune in at https://t.co/rLdeAt7cyx. #HeartMonth https://t.co/6FGXEgv6Wu

HCPs: People with #disabilities are 3 times more likely to have #heartdisease than those without disabilities. In honor of #AmericanHeartMonth, help your patients explore the physical activities suitable for their disability type. bit.ly/2EnsTBx

test Twitter Media - HCPs: People with #disabilities are 3 times more likely to have #heartdisease than those without disabilities. In honor of #AmericanHeartMonth, help your patients explore the physical activities suitable for their disability type. https://t.co/9O33ubwifA https://t.co/SpXpDqLgcP

@Raelove03 CWD and Bovine Spongiform Encephalopathy (BSE, or “Mad Cow Disease”) are both animal prion diseases, a family of rare progressive neurodegenerative disorders. CWD affects deer, elk, reindeer, sika deer and moose, while BSE affects cows.

@Mad_Scientist25 Yes - Chronic Wasting Disease (CWD) is a prion disease that affects deer, elk, reindeer, sika deer and moose. To date, there have been no reported cases of CWD infection in people.

Hunters - be as safe as possible and lower your potential risk of exposure to #ChronicWastingDisease. Take CDC’s recommended steps when hunting in areas with #CWD: bit.ly/2EnQPox.

test Twitter Media - Hunters - be as safe as possible and lower your potential risk of exposure to #ChronicWastingDisease. Take CDC’s recommended steps when hunting in areas with #CWD: https://t.co/aPy5xs4T13. https://t.co/fjxEezzJJt

#lymedisease

@CDC_AMD Hey, can we get more $$$ for research and treatment for #Lymedisease ? Monitoring has done absolutely nothing in regards to testing, treatment, research. It's INSANE that nothing has been done for 40 years about tick borne illnesses.

A negative test does not rule out #LymeDisease Learn more about how to diagnose Lyme here: buff.ly/2sNSHjc

test Twitter Media - A negative test does not rule out #LymeDisease Learn more about how to diagnose Lyme here: https://t.co/OssrqDlLkD https://t.co/4uONqAtSgT

Lyme disease patients (67%) have postponed or avoided medical treatment due to discrimination, disrespect or difficulty obtaining care. #MyLymeData #LymeDisease tinyurl.com/y4rkruvm

test Twitter Media - Lyme disease patients (67%) have postponed or avoided medical treatment due to discrimination, disrespect or difficulty obtaining care. #MyLymeData #LymeDisease https://t.co/Ytok5v5oZl https://t.co/Sfs03xw5Ps

“It gave me a purpose,” she adds of her journey, “and made me find myself all over again.” @AvrilLavigne #LymeDisease #HeadAboveWater people.com/music/avril-la…

#Antiparasitic

Trending

Copyright © 2019. All Rights Reserved. The Human Parasite Support Network.