Tag: Proteins

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The Endoplasmic Reticulum: Networking Inside the Cell

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Like a successful business networker, a cell’s endoplasmic reticulum (ER) is the structure that reaches out—quite literally—to form connections with many different parts of a cell. In several important ways, the ER enables those other parts, or organelles, to do their jobs. Exciting new images of this key member of the cellular workforce may clarify how it performs its roles. Such knowledge will also help studies of motor neuron and other disorders, such as amyotrophic lateral sclerosis (ALS), that are associated with abnormalities in ER functioning.

Structure Follows Function

Illustration of some of the jobs that the ER performs in the cell.

An illustration of some of the jobs that the endoplasmic reticulum (ER) performs in the cell. Some ER membranes (purple) host ribosomes on their surface. Other ER membranes (blue) extending into the cytoplasm are the site of lipid synthesis and protein folding. The ER passes on newly created lipids and proteins to the Golgi apparatus (green), which packages them into vesicles for distribution throughout the cell. Credit: Judith Stoffer.

Initiated in 1965, the Postdoctoral Research Associate Program (PRAT) is a competitive postdoctoral fellowship program to pursue research in one of the laboratories of the National Institutes of Health. PRAT is a 3-year program providing outstanding laboratory experiences, access to NIH’s extensive resources, mentorship, career development activities and networking. The program places special emphasis on training fellows in all areas supported by NIGMS, including cell biology, biophysics, genetics, developmental biology, pharmacology, physiology, biological chemistry, computational biology, immunology, neuroscience, technology development and bioinformatics

The ER is a continuous membrane that extends like a net from the envelope of the nucleus outward to the cell membrane. Tiny RNA- and protein-laden particles called ribosomes sit on its surface in some places, translating genetic code from the nucleus into amino acid chains. The chains then get folded inside the ER into their three-dimensional protein structures and delivered to the ER membrane or to other organelles to start their work. The ER is also the site where lipids—essential elements of the membranes within and surrounding a cell—are made. The ER interacts with the cytoskeleton—a network of protein fibers that gives the cell its shape—when a cell divides, moves or changes shape. Further, the ER stores calcium ions in cells, which are vital for signaling and other work.

To do so many jobs, the ER needs a flexible structure that can adapt quickly in response to changing situations. It also needs a lot of surface area where lipids and proteins can be made and stored. Scientists have thought that ER structure combined nets of tubules, or small tubes, with areas of membrane sheets. However, recent NIGMS PRAT (Postdoctoral Research Associate; see side bar) fellow Aubrey Weigel, working with her mentor and former PRAT fellow Jennifer Lippincott-Schwartz of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (currently at the Howard Hughes Medical Institute in Virginia) and colleagues, including Nobel laureate Eric Betzig, wondered whether limitations in existing imaging technologies were hiding a better answer to how the ER meets its surface-area structural needs in the periphery, the portion of the cell not immediately surrounding the nucleus. Continue reading “The Endoplasmic Reticulum: Networking Inside the Cell”

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Actin’s Many Roles

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Skin cancer cells

Skin cancer cells from a mouse. Credit: Catherine and James Galbraith, Oregon Health and Science University, Center for Spatial Systems Biomedicine, Knight Cancer Institute.

This heart-shaped image shows two mouse skin cancer cells connected to each other with actin, a protein that is part of the cellular skeleton. Researchers use mouse cells like these to tease out the molecular methods that cancer uses to invade new tissues in the body. It turns out that actin plays an essential role.

Cells can move as a collective, or independently. Movement of an individual cell requires a series of carefully controlled steps. Among them, a cell must break contacts with its neighbor cells and change its connections to the proteins and fibers around it. In addition, it must sense and follow a chemical path through the tissue it lies in. To do this, a cell changes shape, molding its membrane into flaps or feet called protrusions reaching in the direction it is traveling. Actin, among a variety of other molecules, is involved in all of these steps, but especially the shape change, when it gathers inside the cell membrane to help form the protrusions. Continue reading “Actin’s Many Roles”

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There’s an “Ome” for That

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In the 13 years since the sequencing of the human genome, the list of “omes” has proliferated. Drop us a comment with your favorite ome—we may feature it in a follow-up post next month.

Have you ever collected coins, cards, toy trains, stuffed animals? Did you feel the need to complete the set? If so, then you may be a completist. A completist will go to great lengths to acquire a complete set of something.

Scientists can also be completists who are inspired to identify and catalog every object in a particular field to further our understanding of it. For example, a comprehensive parts list of the human body—and of other organisms that are important in biomedical research—could aid in the development of novel treatments for diseases in the same way that a parts list for a car enables auto mechanics to build or repair a vehicle.

More than 15 years ago, scientists figured out how to catalog every gene in the human body. In the years since, rapid advances in technology and computational tools have allowed researchers to begin to categorize numerous aspects of the biological world. There’s actually a special way to name these collections: Add “ome” to the end of the class of objects being compiled. So, the complete set of genes in the body is called the “genome,” and the complete set of proteins is called the “proteome.”

Below are three -omes that NIH-funded scientists work with to understand human health.

Genome

Illustration of the entire outer shell of the bacteriophage MS2. Credit: Wikimedia Commons, Naranson.

The genome is the original -ome. In 1976, Belgium scientists identified all 3,569 DNA bases—the As, Cs, Gs and Ts that make up DNA’s code—in the genes of bacteriophage MS2, immortalizing this bacteria-infecting virus as possessing the first fully sequenced genome.

Over the next two decades, a small handful of additional genomes from other microorganisms followed. The first animal genome was completed in 1998. Just 5 years later, scientists identified all 3.2 billion DNA bases in the human genome, representing the work of more than 1,000 researchers from six countries over a period of 13 years. Continue reading “There’s an “Ome” for That”

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Newly Identified Cell Wall Construction Workers: A Novel Antibiotic Target?

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SEDS

A family of proteins abbreviated SEDS (bright, pink) help build bacterial cell walls, so they are a potential target for new antibiotic drugs. Credit: Rudner lab, Harvard Medical School.

Scientists have identified a new family of proteins that, like the targets of penicillin, help bacteria build their cell walls. The finding might reveal a new strategy for treating a range of bacterial diseases.

The protein family is nicknamed SEDS, because its members help control the shape, elongation, division and spore formation of bacterial cells. Now researchers have proof that SEDS proteins also play a role in constructing cell walls. This image shows the movement of a molecular machine that contains a SEDS protein as it constructs hoops of bacterial cell wall material.

Any molecule involved in building or maintaining cell walls is of immediate interest as a possible target for antibiotic drugs. That’s because animals, including humans, don’t have cell walls—we have cell membranes instead. So disabling cell walls, which bacteria need to survive, is a good way to kill bacteria without harming patients.

This strategy has worked for the first antibiotic drug, penicillin (and its many derivatives), for some 75 years. Now, many strains of bacteria have evolved to resist penicillins—and other antibiotics—making the drugs less effective.

According to the Centers for Disease Control and Prevention, drug-resistant strains of bacteria Exit icon infect at least 2 million people, killing more than 20,000 of them in the U.S. every year. Identifying potential new drug targets, like SEDS proteins, is part of a multi-faceted approach to combating drug-resistant bacteria.

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Pigment Cells: Not Just Pretty Colors

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If you’ve ever visited an aquarium or snorkeled along a coral reef, you’ve witnessed the dazzling colors and patterns on tropical fish. The iridescent stripes and dots come from pigment cells, which also tint skin, hair and eyes in all kinds of animals, including humans. Typically, bright colors help attract mates, while dull ones provide camouflage. In humans, pigment helps protect skin from DNA-damaging UV light.

Researchers study cellular hues not only to decipher how they color our world, but also to understand skin cancers that originate from pigment cells. Some of these researchers work their way back, developmentally speaking, to focus on the type of cell, known as a neural crest cell, that is the precursor of pigment cells.

Present at the earliest stages of development, neural crest cells migrate throughout an embryo and transform into many different types of cells and tissues, including nerve cells, cartilage, bone and skin. The images here, from research on neural crest cells in fish and salamanders, showcase the beauty and versatility of pigment cells in nature’s palette.

Xanthophores
Pigment cells called xanthophores, shown here in the skin of the popular laboratory animal zebrafish, glow brightly under light. Credit: David Parichy, University of Washington.
Melanocytes
Dark pigment cells, called melanocytes, like these in pearl danio, a tropical minnow and relative of zebrafish, assemble in skin patterns that allow the animals to blend into their surroundings or attract mates. Credit: David Parichy, University of Washington.
Fin of pearl danio
Pigment cells can form all sorts of patterns, like these stripes on the fin of pearl danio. Credit: David Parichy, University of Washington.
Salamander skin
Pigment cells arise from neural crest cells. Here, pigment cells can be seen migrating in the skin of a salamander where they will form distinct color patterns. Credit: David Parichy, University of Washington.

 

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A Labor Day-Themed Collection: Hard-Working Cell Structures

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Hard labor might be the very thing we try to avoid on Labor Day. But our cells and their components don’t have the luxury of taking a day off. Their non-stop work is what keeps us going and healthy.

Scientists often compare cells with small factories. Just like a factory, a cell contains specialized compartments and machines—including organelles and other structures—that each play their own roles in getting the job done. In the vignettes below, we give a shout out to some of these tireless cellular workers.

Energy Generators
Credit: Thomas Deerinck, National Center for Microscopy and Imaging Research
Mitochondria are the cell’s power plants. They convert energy from food into a molecule called ATP that fuels virtually every process in the cell. As shown here, mitochondria (brown) often have distinct, oblong shapes. Like most other organelles, mitochondria are encased in an outer membrane. But they also have an inner membrane that folds many times, increasing the area available for energy production. In addition, mitochondria store calcium ions, help make hemoglobin—the vital iron-containing protein that allows red blood cells to carry oxygen—and even take part in producing some hormones. Defects in mitochondria can lead to a host of rare but often incurable diseases that range from mild to devastating. Researchers are studying mitochondria to better understand their manifold jobs in the cell and to find treatments for mitochondrial diseases.

Continue reading “A Labor Day-Themed Collection: Hard-Working Cell Structures”

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Protein Paradox: Enrique De La Cruz Aims to Understand Actin

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Enrique M. De La Cruz
Credit: Jeff Foley, American Heart Association.
Enrique M. De La Cruz
Grew up in: Newark and Kearny, New Jersey
Job site: Yale University
Favorite food: His mom’s Spanish-style polenta (harina de maíz)
Alternative career: Managing a vinyl record shop
Favorite song: “Do Anything You Wanna Do” by Eddie & The Hot Rods

Enrique De La Cruz stood off to the side in a packed room. As he waited for his turn to speak, he stroked the beads of a necklace. Was he nervous? Quietly praying? When he took center stage, the purpose of the strand became clear.

Like a magician—and dressed all in black—De La Cruz held up the necklace with two hands so everyone, even those sitting in the back, could see it. It was made of snap-together beads. De La Cruz waved the strand. It wiggled in different directions. Then, with no sleight of hand, he popped off one of the beads. The necklace broke into two.

For the next hour, De La Cruz pulled out one prop after another: a piece of rope from his pocket, a pencil tucked behind his ear and even a fresh spear of asparagus stuffed in his backpack. At one point, De La Cruz assembled a conga line with people in the front row. Continue reading “Protein Paradox: Enrique De La Cruz Aims to Understand Actin”

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The Proteasome: The Cell’s Trash Processor in Action

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Our cells are constantly removing and recycling molecular waste. On the occasion of Earth Day, we put together this narrated animation to show you one way cells process their trash. The video features the proteasome, a cellular machine that breaks down damaged or unwanted proteins into bits that the cell can re-use to make new proteins. For this reason, the proteasome is as much a recycling plant as it is a garbage disposal.

For more details about the proteasome and other cellular disposal systems, check out our article How Cells Take Out the Trash.

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Seeing Telomerase’s ‘Whiskers’ and ‘Toes’

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Telomerase and its components.

The image here is the “front view” of telomerase, with the enzyme’s components shown in greater detail than ever before. Credit: UCLA Department of Chemistry and Biochemistry.

Like the features of a cat in a dark alley, those of an important enzyme called telomerase have been elusive. Using a combination of imaging techniques, a research team led by Juli Feigon Exit icon of the University of California, Los Angeles, has now captured the clearest view ever of the enzyme.

Telomerase maintains the DNA at the ends of our chromosomes, known as telomeres, which act like the plastic tips on the ends of shoelaces. In the absence of telomerase activity, telomeres get shorter each time our cells divide. Eventually, the telomeres become so short that the cells stop dividing or die. On the other hand, cells with abnormally high levels of telomerase activity can constantly rebuild their protective chromosomal caps. Telomerase is particularly active within cancer cells. Continue reading “Seeing Telomerase’s ‘Whiskers’ and ‘Toes’”

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Structural Studies Demystify Membrane Protein

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Animated structural model of TSPO.
Animated structural model of TSPO. Credit: Michigan State University.

Mitochondria have proteins that span their membranes to control the flow of messages and materials moving into and out of the organelle. One way scientists can learn more about how membrane proteins function—and how medicines might interact with them—is to determine their structures. But for a variety of reasons, obtaining the structures has been notoriously difficult.

Two structural studies have now shed light on the mysterious mitochondrial membrane protein TSPO. This protein plays a key role in transporting cholesterol and drugs into the cell’s mitochondria. While here, the cholesterol is converted to steroid hormones that are essential for numerous bodily functions. Although many researchers have been studying TSPO since the 1990s, they’ve remained uncertain about its mechanisms and how it truly functions. Continue reading “Structural Studies Demystify Membrane Protein”