Harris Lecture 8 notes (1 per page)

Harris Lecture 8 notes (1 per page) - Signaling via small...

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1 1 Signaling via small molecules 1. Independently of plasma membrane proteins 2. Through plasma membrane channels 3. Downstream of plasma membrane G-protein coupled receptors
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2 2 Which class of molecules could signal from outside to inside the cell without a channel or receptor? A B C D
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3 3 A very small signaling molecule: Nitric oxide (NO) Made by the deamination of arginine by NO synthases Acts locally because of a 5-10 second half life Affects smooth muscle and other target cells Nitroglycerine is used to treat heart pain It is converted to NO and relaxes blood vessels, reducing workload on the heart
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4 4 Small hydrophobic signaling molecules Steroid hormones -made from cholesterol -affect sexual characteristics and metabolism Thyroid hormones -made from tyrosine -increase metabolic rate Retinoids -made from Vitamin A -regulate development Vitamin D -affects metabolism Transported in extracellular fluids by carrier proteins Dissociate from carriers upon cell entry In the cell they bind a member of the nuclear receptor superfamily
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5 5 The nuclear receptor superfamily Contain binding sites for a small hydrophobic molecule and for DNA 48 identified in the human genome More than half only identified based on sequence analyses Æ their ligands are unknown Æ termed >
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6 6 Ligand binding alters receptor conformation, and releases inhibitors, to promote DNA binding and downstream transcription
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7 7 Ligand binding alters receptor conformation, and releases inhibitors, to promote DNA binding and downstream transcription
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8 8 The transcriptional response to hormones can be complex
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9 9 Signaling via small molecules 1. Independently of plasma membrane proteins 2. Through plasma membrane channels 3. Downstream of plasma membrane G-protein coupled receptors
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10 10 Ion channels are a major class of signaling molecules
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Harris Lecture 8 notes (1 per page) - Signaling via small...

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