Membranes and cell signalling.pdf

Cell signalling  What is cell signalling? It describes communication between cells It usually involves a chemical messenger (signal/ligand), released by the signalling cell The signal is detected by the responding cell (receptor) Signal detection triggers i...

Cell signalling  What is cell signalling? It describes communication between cells It usually involves a chemical messenger (signal/ligand), released by the signalling cell The signal is detected by the responding cell (receptor) Signal detection triggers intracellular reactions that influence the behaviour of the responding cell  The task(s) of cell communication Signal release – synthesis and excretion of the signalling molecule Signal detection – interaction of signal and receptor Signal transduction – translation of detection to changes in cell physiology or gene expression  Signals Paracrine - Acts on local set of cells Autocrine - Acts on the secreting cell Endocrine - long range signals moving through the blood stream  Signalling and control of gene expression Cell-cell signalling can change the repertoire of transcription factors in the responding cell, resulting in different gene expression  Some signals can form gradients Cell fate depends upon signal concentration!!! Secreting cells High Signal concentration Low  How does the signal enter the cell? Two Strategies: 1. The signal can pass through the plasma membrane -Nuclear receptors 2. The signal can activate a membrane receptor -G protein linked receptors -Serine/threonine kinase receptors  Nuclear receptors The signals are steroids or retinoids These signals can pass through the plasma membrane In the cytoplasm they encounter nuclear receptors This complex then enters the nucleus to activate genes  Signalling through nuclear receptors Nuclear receptors like the glucocorticoid receptor are cytoplasmic proteins – In their inactive form, they are bound to Hsp chaperones – Ligand binding releases the Hsp – The receptor-ligand complex moves to the nucleus to activate the transcription of target genes  G-protein linked receptors Transmembrane receptors are linked to a G-protein Upon ligand binding the G protein releases GDP and takes up GTP Ga dissociates from Gbg and activates downstream 'second messengers' (eg cAMP) GTP is hydrolysed to GDP and Ga reassociates with Gbg  Serine/threonine Kinase receptors Transmembrane receptors that bind the TGFb family of signals Ligand brings together type I and type II receptors II phosphorylates I Smads become phosphorylated and move into the nucleus to act as transcription factors