Кері сигнал: Биологияда сигнал көзіне қайту процесі

In biology, a signal traveling backwards to its source
Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, instead of signals leaving the nucleus, they are sent to the nucleus. In cell biology, this type of signaling typically occurs between the mitochondria or chloroplast and the nucleus. Signaling molecules from the mitochondria or chloroplast act on the nucleus to affect nuclear gene expression. In this regard, the chloroplast or mitochondria act as a sensor for internal external stimuli which activate a signaling pathway.

Retrograde signals are transmitted from plastids to the nucleus in plants and eukaryotic algae, and from mitochondria to the nucleus in most eukaryotes. Retrograde signals are generally considered to convey intracellular signals related to stress and environmental sensing. Many of the molecules associated with retrograde signaling act on modifying the transcription or by directly binding and acting as a transcription factor. The outcomes of these signaling pathways vary by organism and by stimuli or stress. Originally believed to be photosynthetic bacteria, the mitochondria and chloroplast transferred some of their DNA to the membrane protected nucleus. Thus, some of the proteins required for the mitochondria or chloroplast are within the nucleus. This transfer of DNA further required a network of communication to properly respond to external and internal signals and produce requisite proteins.

The first retrograde signaling pathways discovered in yeast is the RTG pathway. The RTG pathway plays an important role in maintaining the metabolic homeostasis of yeast. Retrograde signaling form the mitochondria initiates production precursor molecules of glutamate to properly balance supplies within the mitochondria. Retrograde signaling can also act to arrest growth if problems are encountered. In Saccharomyces cerevisiae, if the mitochondria fails to develop properly, they will stop growing until the issue is addressed or cell death is induced. These compounds, previously believed to be damaging to the cell, have since been discovered to act as a signaling molecule. Reactive oxygen species are created as a by product of aerobic respiration and act on genes involved in the stress response. By doing this, surrounding cells are "primed" to react to the stress because genes involved in stress response are initiated prior to encountering the stress.

The primary purpose of retrograde neurotransmission is regulation of chemical neurotransmission. Additionally, retrograde signaling initiates a signaling cascade that focuses on the presynaptic neuron. Once retrograde signaling is initiated, there is an increase in action potentials that begin in the presynaptic neuron, which directly impacts the postsynaptic neuron by increasing the number of its receptors. Endocannabinoids like anandamide are known to act as retrograde messengers, as is nitric oxide. Retrograde signaling may also play a role in long term potentiation (LTP), a proposed mechanism of learning and memory, although this is controversial.

In 2009, Regehr et al. proposed criteria for defining retrograde neurotransmitters. According to their work, a signaling molecule can be considered a retrograde neurotransmitter if it satisfies all of the following criteria:

The retrograde neurotransmitter, nitric oxide (NO) is a soluble gas that can readily diffuse through various cell membranes. Nitric oxide synthase is the enzyme responsible for the synthesis of NO in various presynaptic cells. Specifically, NO is known to play a critical role in LTP, which plays an important role in memory storage within the hippocampus. Additionally, literature suggests that NO can act as intracellular messengers in the brain and can also have an effect on the presynaptic glutamatergic and GABAergic synapses. Utilizing retrograde signaling, endocannabinoids, a type of retrograde neurotransmitter, are activated when they bind to G protein coupled receptors on the presynaptic terminals of neurons. The activation of endocannabinoids results in the release of particular neurotransmitters at the excitatory and inhibitory synapses of a neuron, ultimately impacting various forms of plasticity.

Long term potentiation is the persistent increase in the strength of a chemical synapse that lasts from hours to days. It is thought to occur via two temporally separated events, with induction occurring first, followed by expression. Another is that it releases a preformed retrograde messenger upon such activation. Yet another mechanism is that synapse spanning proteins may be altered by LTP inducing stimuli in the postsynaptic cell, and that changes in conformation of these proteins propagates this information across the synapse and to the presynaptic cell.

Of these mechanisms, the retrograde messenger hypothesis has received the most attention. Among proponents of the model, there is disagreement over the identity of the retrograde messenger. A flurry of work in the early 1990s to demonstrate the existence of a retrograde messenger and to determine its identity generated a list of candidates including carbon monoxide, platelet activating factor, arachidonic acid, and nitric oxide. Nitric oxide has received a great deal of attention in the past, but has recently been superseded by adhesion proteins that span the synaptic cleft to join the presynaptic and postsynaptic cells. The endocannabinoids anandamide and/or 2 AG, acting through G protein coupled cannabinoid receptors, may play an important role in retrograde signaling in LTP.