Name: light control of the biological clock
Uploaded: 2021-04-07T12:11:59.000Z
Duration: 2 min 19 s
Channel: JoVE

Nearly all living organisms from microorganisms to mammals synchronize their behavioral, biochemical, and physiological processes according to the 24-hour solar cycle, or the circadian clock.
The circadian clock is primarily controlled by specific machinery, and in mammals, the suprachiasmatic nucleus present in the hypothalamus acts as a master clock and controls circadian rhythms throughout the body.
However, most cells in the body also have an internal circadian rhythm. A cyclic pattern of expression of genes in these cells guides the circadian clock at the organism level.
The underlying genetics of the circadian rhythms at the cellular level have classically been studied in Drosophila, where a set of clock genes regulate the cell circadian rhythm through a negative feedback loop.&#160;
During the day time, the transcription factors, Clock and Cycle heterodimerize and activate the transcription of their target genes, including the Period gene, also known as Per.
The Per protein dimerizes with another protein called Timeless, or Tim. However, both these proteins are not very stable in the presence of light and are subsequently degraded by a proteasome.
During the evening, the stable Per/Tim complex can accumulate in the cell cytoplasm and then translocate to the nucleus - where it binds to the Clock-Cycle dimer, and removes it from DNA- thereby, inhibiting its transcriptional activity.
In addition to this negative feedback regulation, other regulatory proteins in the cell also participate in the modulation of the activity of Clock.
For example, Clockwork Orange is a transcriptional repressor that co-represses Clock-cycle transcriptional activity along with Per by competing for the binding site on DNA.
Since circadian rhythms play an essential role in coordinating normal body functioning, any disruption to it can lead to minor to severe diseases, including metabolic syndromes and inflammatory diseases, as well as cancer.

circadian rhythms and gene regulation

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin B&#252;nning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years, many other associated genes were identified, and the mechanism of regulation of the circadian rhythms was further unraveled. The contribution of Jeffrey C. Hall, Michael Rosbash, and Michael W. Young to the understanding of the internal biological circadian clocks was recognized with the Nobel Prize for Physiology or Medicine in 2017.
<h4>The Molecular Mechanism of Circadian Rhythms</h4>
In Drosophila, the Period (PER) protein is the main regulatory protein that controls the internal circadian rhythms in cells. PER forms a complex with another essential protein called Timeless (TIM) and enters the nucleus. Here, it can regulate the levels of PER expression in the cell through feedback inhibition. Additionally, it also controls the expression of other genes by inhibiting the activity of the transcriptional activators Clock and Cycle. Importantly, the stability of the PER/TIM complex is dependent on the presence or absence of light, meaning it is degraded under daytime conditions. The result is that the expression of genes downstream of the PER/TIM complex is controlled by light, and this phenomenon allows for synchronization of the circadian clock.
In mammals, the regulation of the circadian rhythm works in a very similar manner. However, due to the addition of several paralog genes, the regulation of the entire pathway is much more complicated than in Drosophila.
<h4>Significance of Circadian Rhythms </h4>
All living organisms on Earth have evolved in the presence of 24-hour day/night cycles and adapted their cellular, physiological as well as behavioral responses accordingly. For example, the diurnal cycles of sleeping and waking, body temperature, and hormone release in mammals are controlled by the circadian rhythms. Irregular circadian rhythms can lead to many health issues, such as bipolar disorder or sleep disorders. Additionally, disruption of circadian rhythms can result in adverse effects on other systems of the body, including the cardiovascular system.

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and ...

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Cell Signaling Pathways

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light control of the biological clock

Light helps control the biological clock by shaping circadian rhythms. These 24-hour cycles affect how cells, body systems, and behavior stay in sync with day and night. In animals, this timing system helps regulate complex physiology.

The study of circadian rhythm began in 1935, when German zoologists Hans Kalmus and Erwin Bünning found it in Drosophila melanogaster, the fruit fly. The molecular basis stayed unclear for decades. In 1984, Jeffrey C. Hall, Michael Rosbash, and Michael W. Young showed that Per gene expression rises and falls over a 24-hour cycle. Later work identified more related genes and clarified how the clock is controlled. Their work on internal biological clocks was recognized with the 2017 Nobel Prize in Physiology or Medicine.

In Drosophila, the Period protein, or PER, is the main regulator of circadian timing in cells. PER joins with another protein called Timeless, or TIM, and the pair enters the nucleus. There, it uses feedback inhibition to reduce PER expression. It also blocks the transcriptional activators Clock and Cycle, which lowers the expression of other genes.

Light affects the stability of the PER/TIM complex. Under daytime conditions, the complex is degraded. This makes gene expression downstream of PER and TIM depend on light and helps synchronize the circadian clock. A similar system works in mammals, but several paralog genes make the pathway more complex than it is in Drosophila.

Circadian rhythms matter because organisms evolved under daily light and dark cycles. In mammals, they help control sleep and waking, body temperature, and hormone release. When circadian rhythms become irregular, health problems can follow. These may include sleep disorders and bipolar disorder, and disruption can also affect the cardiovascular system.

Light Control of the Biological Clock

notch signaling pathway

Notch Cell Communication and Gene Control

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canonical wnt signaling pathway

Wnt Signals in Development and Disease

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hedgehog signaling pathway

Hedgehog Signaling in Growth and Disease

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nf-&#954;b-dependent signaling pathway

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NF-κB is a transcription factor that helps control immune defense and inflammation in animals. It was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore because of its interaction with the immunoglobulin light chain enhancer in B-cells. Since then, researchers have shown that NF-κB regulates the expression of more than 100 genes. Many of the genes controlled by NF-κB support innate and adaptive immune responses. They also help drive inflammatory responses. In this way,...

internal receptors

Internal Receptors and Hormone Signals

Internal receptors are proteins inside a cell that bind signaling molecules. These receptors help certain hormones send messages after they pass through the cell membrane. Because the receptor is internal, the signal acts from within the cell rather than at the surface. Many internal receptors respond to steroid hormones. These hormones can cross the membrane and reach the receptor inside the cell. Once the hormone binds, the receptor can help trigger a response that changes cell activity. <br...

Light helps control the biological clock by shaping circadian rhythms. These 24-hour cycles affect how cells, body systems, and behavior stay in sync with day and night. In animals, this timing system helps regulate complex physiology. The study of circadian rhythm began in 1935, when German zoologists Hans Kalmus and Erwin Bünning found it in Drosophila melanogaster, the fruit fly. The molecular basis stayed unclear for decades. In 1984, Jeffrey C. Hall, Michael Rosbash, and Michael W. Young...

what is cell signaling?

Cell Signaling in Cell Communication

Cell signaling is a key part of cell communication. It helps cells send, receive, and respond to signals so they can work together. A signal starts when a cell releases a molecule. Another cell detects that molecule with a receptor, which is a protein that binds the signal. This binding begins a signaling pathway inside the cell. The pathway carries the message through the cell in a process called signal transduction. In the end, the cell produces a response. That response can change cell...

autocrine signaling

Autocrine Cell Communication

Autocrine cell communication is a signaling process in which a cell sends a message to itself. In this pathway, the cell releases a signaling molecule and also has receptors that can detect that same molecule. This makes the cell both the sender and the receiver. Autocrine signaling is common in cell communication and is often grouped with cytokine signaling. Cytokines are small signaling proteins that help cells communicate, especially in immune responses and growth control. In autocrine...

paracrine signaling

Local Cell Communication in Tissues

Paracrine signaling is a form of local cell communication in tissues. In this process, one cell releases chemical signals that affect nearby target cells. Because the signal stays close to where it is made, paracrine signaling helps cells coordinate responses within a limited area. These signals do not travel far through the body. Instead, they move through the space around neighboring cells and bind to specific receptors on target cells. This nearby action makes paracrine signaling different...

endocrine signaling

Hormones in Endocrine Signaling

Endocrine signaling uses hormones to send messages through the body. These signals travel through the bloodstream from one cell or gland to another target cell. The target cell responds only if it has the right receptor to detect the hormone. This type of cell communication helps coordinate many body functions at a distance. Because the signal moves through the blood, the source and the target do not need to be close together. Endocrine signaling is a key way cells regulate activity in other...

what are second messengers?

Cell Signals and Second Messengers

Second messengers are small molecules that help cells pass along signals after a receptor is activated. They carry the message inside the cell and help start a response to the outside signal. This signaling step is important in cell communication. It helps the signal move from the cell membrane to targets deeper inside the cell. Second messengers make that relay possible and help the cell respond in a controlled way. Common second messengers include cyclic AMP, calcium ions, and inositol...

intracellular signaling cascades

Cell Signaling Cascades Inside Cells

Cell signaling cascades inside cells relay messages from one molecule to the next. These pathways help a cell respond to a signal in a controlled way. The signal is often carried through a series of steps, which can amplify the original message. A signaling cascade may involve a receptor at the cell surface and molecules inside the cell that pass the message along. Each step can trigger the next step in the chain. This makes the response specific and allows the cell to act on the signal at the...

g-protein coupled receptors

G-protein Receptors in Cell Signaling

G-protein coupled receptors help cells receive and pass along signals. These membrane receptors sit in the cell membrane and respond when a ligand binds to them. A ligand is a molecule that fits and attaches to a receptor. When a ligand binds, the receptor changes shape. That shape change activates a G protein inside the cell. The G protein then helps start the signal inside the cell. These receptors are important because they connect outside signals to inside responses. They are a major part...

enzyme-linked receptors

How Enzyme-Linked Receptors Signal

Enzyme-linked receptors help cells respond to signals outside the cell. They are a major class of cell-surface receptors, and they work by triggering enzyme activity after a signal binds. Many enzyme-linked receptors are receptor tyrosine kinases. When a signaling molecule binds, the receptor changes shape and activates its enzyme side. This starts a signaling step inside the cell that can affect cell behavior. These receptors are important in cell communication. They help carry messages from...

non-canonical wnt signaling pathways

Wnt Pathways That Guide Cell Position

Wnt signaling helps guide early embryonic development and later life processes in animals. It is controlled by Wnt proteins, which can trigger different intracellular pathways depending on which receptors and co-receptors they bind. These signals support organ formation in the embryo and help maintain neuronal and blood stem cells. The non-canonical Wnt pathways are the β-catenin independent routes. They are more diverse and less well characterized than the canonical Wnt/β-catenin pathway. Two...

key terms and concepts

Learn how light, PER and TIM proteins, and feedback inhibition keep circadian rhythms on a 24-hour cycle in fruit flies and mammals.

Light Control of the Biological Clock | JoVE K12

molecular biology

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Light Control of the Biological Clock

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