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Lecture 9

Lecture 9 Notes.docx

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Department
Biology
Course
Biology 2382B
Professor
Robert Cumming
Semester
Winter

Description
Cell Biology Lecture 9 Notes – Basic Principles of cell signaling and GPCR system Basic Elements of cell signaling:  Signal or signaling molecule (ligand, first messenger) o Small molecules (epinephrine, acetylcholine, steroids), peptides, hormones, & light secreted by signaling cells o First messenger – molecule brings first message to the cell to do something  Receptors – recognize the signal o Cell-surface receptors o Intracellular receptors  Intracellular signaling and effector proteins o Receptors activated and instigate a sequence of events in the cell o G proteins, protein kinases (phosphorylate amino acids – serine, tyrosine, thymine) and phosphates  Second messengers o Small molecules such as Ca2+, cAMP, cGMP, IP3, DAG, NO  All cells receive and respond to signals from their environment – cells and environment must communicate Four forms of intercellular signaling:  Signaling molecules can be delivered to the cell by different mechanisms  Endocrine = signaling to distant cells o Signaling molecules are synthesized & secreted by signaling cells (endocrine cells) & are transported through circulatory system to target cells o The hormone generally refers to signaling molecules that mediate endocrine signaling  Paracrine = signaling to nearby cells o The signaling molecules released by a cell affect only those target cells in close proximity o E.g. neurotransmitters  Autocrine = signaling to cell itself o Cells respond to substances that they themselves release o Have receptor & recognize signal & develop response to signal molecule o E.g. tumour cells – express receptors for different growth factors  Signaling by PM-attached proteins o Signal molecules are membrane attached proteins o Make a cell complex – not like a cell-adhesion – cell complex just based on interactions between signal molecule and the cell Ligand-receptor interactions:  Binding specificity is based on the molecular complementarity (molecular recognition) between the interacting surfaces of a receptor (binding interface) and ligand (non-covalent forces) o Surfaces that interact tightly = complementary to each other  Interactions trigger a conformational change in the receptor – becomes active  Very often signaling molecules (ligands) induce receptor dimerization The Dissociation Constant:  R + L  RL at equilibrium we have a simple equilibrium-binding equation: K d [R][L]/[RL] o Kdis the measure of affinity of a receptor to its ligand o Kdis ligand concentration required to bind 50% of cell surface receptors o The lower the Kd, the lower the ligand concentration required to occupy 50% of the cell surface receptors  Ligand binding to a receptor usually can be viewed as a simple reversible reaction Nuclear-receptor superfamily:  Specific type of receptors that are NOT located in the membrane – cytoplasm or nucleus  Transcription factors that are activated once they bind their appropriate ligand  Focus only on the domains of the general primary structure  Lipid-soluble molecules/ hormones bind to intracellular receptors which constitute the nuclear receptor superfamily of transcription factors o Steroid hormones are extracellular & are used by intracellular receptor to mediate cell response – are synthesized by adrenal glands  Ligand binding domain – binds to specific hormones  DNA binding domain – binding the specific DNA sequence (response element)  Variable region – significant difference between transcription factors – have one of several activation domains within the variable region Gene activation by a nuclear receptor:  GR is a steroid hormone – can diffuse through PM and get inside the cell because is lipid soluble o Is a potent anti-inflammatory/ immuno-suppressive reagent & others  The characteristic nucleotide sequences of the DNA sites that bind nuclear receptors are called response elements o The receptor binds to a response element of the target gene and stimulate
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