Thermoregulation: an orphan receptor finds its way in the cold

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...

The human body has a sophisticated thermoregulation system that employs negative feedback mechanisms to maintain an optimal core temperature. When the core temperature drops, peripheral and central thermoreceptors send signals to the hypothalamus, activating the heat-promoting center. This center triggers several responses aimed at increasing the core temperature. First, vasoconstriction reduces the flow of warm blood from internal organs to the skin so that the heat is not lost from the skin,...

Hyperthermia occurs when the body's temperature becomes unusually high, often due to heat exposure, intense physical activity, or certain illnesses. This condition can create a dangerous cycle where elevated body temperature increases the metabolic rate, generating more heat and potentially leading to organ failure and brain damage. A severe form of hyperthermia, called heat stroke, can raise body temperature to life-threatening levels. Fever, on the other hand, is a controlled form of...

The body's temperature, measured in degrees, is determined by the balance between heat production and dissipation to the surrounding environment. For instance, if exercising vigorously, the body will produce more heat, causing sweat and dissipating that heat. Despite extreme environmental conditions and physical exertion, the human temperature-control system maintains a constant core body temperature (the temperature of deep tissues, which are the tissues located beneath the skin and other...

Body temperature reflects the equilibrium between heat production and heat loss within the body. Most heat is generated by metabolically active tissues, particularly the liver, heart, brain, kidneys, and endocrine organs. At rest, skeletal muscles contribute 20–30% of total heat production, but during vigorous exercise, this can increase up to 30–40 times.
The average body temperature is approximately 37°C (98.6°F) and typically ranges from 36.1–37.2°C (97–99°F), remaining relatively stable...

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...