Lecture 15: Cell Signaling pt. 1

4 types of cell signaling

1. direct cell-cell signaling

2. endocrine signaling

3. paracrine signaling

4. autocrine signaling

direct cell-cell signaling example

delta/notch signaling

endocrine signaling examples

• adrenaline

• insulin

• steroid hormone

• estrogen

paracrine signaling example

neurotransmitter

autocrine signaling example

immune response

acetylcholine

a nuerotransmitter

acetylcholine in heart muscle

• relaxes heart muscle

• opens K+ channel and causes hyperpolarization of membrane

  • K+ flows outside cell

heart muscle receptor

muscarinic receptor

acetylcholine in salivary glands

causes saliva secretion

acetylcholine in skeletal muscles

• causes muscle contraction

• opens Na+ channel and causes depolarization of membrane which triggers action potential Ca2+ channel to open

  • Na+ flows inside cell

  • Ca2+ channel opens in sarcoplasmic reticulum, increased Ca2+ causes muscle contraction

skeletal muscle receptor

nicotinic receptor

two types of signaling molecules

1. two large or hydrophilic to cross plasma membrane (majority)

   1. binds to cell surface receptors which generate intracellular signaling

2. small and hydrophobic enough to pass plasma membrane (minority)

   1. binds to receptors inside target cell

large and hydrophilic signaling molecules examples

• conventional neurotransmitters

• peptides

• lipids

small and hydrophobic signaling molecules examples

• steroid hormones

• non-steroid hormones

• dissolves gasses (like nitric oxide)

nuclear receptor of steroid/non-steroid hormones

transcription factors that bind DNA, therefore regulate gene expression

examples of steroid hormone

• testosterone

• estrogen

• progesterone

• glucocorticoids m

• mineralosteoids

examples of non-steroid hormone

• thyroid hormone

• vitamin D3

• retinoic acid

glucocorticoid

stimulate glucose production

nitric oxide (NO) type of signaling

• paracrine signaling

  • acts local

  • short half life

  • it is rapidly converted to nitrates and nitrites

how to synthesize nitric oxide (NO)

from arginine

nitric oxide (NO) signaling cascade

• acetylcholine is released from neuron terminal, which binds to endothelial cells and releases NO

• NO enters smooth muscle cell and reacts with iron in the active site of the guanylyl cyclase

• increases cGMP level and cause blood vessels to dilate, smooth muscle relaxes

types of neurotransmitter membrane receptors

• ligand gated channels → change ion flux

• G-protein coupled receptors → many responses

PDGF signaling

platelet derived growth factor, plays an important role in wound healing

aspirin signaling cascade

inhibits the synthesis of prostaglandin by inhibiting enzyme COX, therefore reduces blood platelet aggregation, inflammation, and smooth muscle contraction

signaling pathway of glucocorticoid

• glucocorticoid diffuses across the plasma membrane

• glucocorticoid in the nucleus binds to receptor which is released from Hsp90

• the receptor dimerizes

• complex assembles with histoneacetyltransferase (HAT) on target DNA

  • HAT acetylates histones, “opening” DNA

• result: transcription of hormone inducible genes such as genes involved in immune response