1. Cell fate Flashcards
Describe the importance of cellular signalling
Cells must have constant signalling to avoid apoptosis. Some signals are required for the cell to simply survive, some signals (additional to the survival signals) are required for differentiation and proliferation. The absence of signals will cause the cell to undergo apoptosis
Give examples of how cellular signalling may effect differentiation
Lung bed epithelium cultured alone causes no differentiation
Lung bed epithelium cultured with intestinal mesenchyme causes differentiation to vili
Lung bed epithelium cultured with stomach mesenchyme causes differentiation to gastric glands.
Describe the four types of cellular induction
Negative: The cells restrict potential of each other
Instructive: The interaction causes the responder cell to become another cell type
Permissive: The reponder cells already contain the potential to differentiate, it simply needs the required environment (e.g. ECM)
Reciprocal: tissues signal each other, which causes differentiation of both tissues: therefore there is no responder or inducer cell, the two cells both give and receive signals.
What are four ways of intercellular signalling?
Contact dependent
Paracrine
Synaptic
Endocrine
Describe contact-dependent intercellular signalling
The signal molecule (ligand) is membrane-bound on the signalling cell. It reacts with a receptor on the target cells
Describe paracrine intercellular signalling
The signalling cell secretes the signalling molecule, which reaches several nearby cells
Describe synaptic intercellular signalling
The signalling molecule (neurotransmitter) is released into a synapse, in which the target cell binds to the signalling molecule
Describe endocrine intercellular signalling
The signalling molecules are released into the bloodstream, and they are transported through the body to stimulate the target cells, which are futher away from the secreting endocrine cell
Describe the general intracellular pathway that is initated upon binding of a ligand to a membrane-bound receptor
When a receptor protein is stimulated by an extracellular signal molecule, an intracellular pathway is initiated. The active receptor activates traget proteins. Examples of target protein is metabolic enzyme (which alters metabolism), a gene regulatory protein (which alters gene expression), or a cytoskeletal protein which alteres cell shape or movement)
Define the type of receptor that signal molecules bind to, according to their hydrophobicity/hydrophility
Hydrophilic signal molecules cannot pass the phospholipid cell membrane, so they bind to surface receptors
Hydrophobic/hydrophilic signal molecules may pass the phospholipid cell membrane, so they bind to intracellular receptors
How are hydrophobic signal molecules transported in the blood?
They are bound to a carrier protein, until the signal molecule is released to pass through the cell membrane
What is the nuclear receptor superfamily and what is its function?
A group of receptors that have a DNA-binding domain and a ligand-binding domain, as well as, a transcription-activating domain. Their function is transcriptional regulation to control expression of genes involved in development, homeostasis and metabolism
Describe the physiology of activation of nuclear receptors
When the ligand binds to the receptor, a conformational change occurs in the receptor, such that the DNA-binding domain binds to a specific DNA sequence in the genome. This DNA sequence that is binds to is the receptor-binding element of the DNA. This results in an up- or down regulation of gene expression
Give examples of receptors in the nuclear receptor superfamily
Cortisol receptor
Estrogen receptor
Progesterone receptor
Vitamin D receptor
Thyroid receptor
Describe the intracellular pathway of steroid hormones
The steroid hormone is transported through the cell membrane (because it is fat soluble). Since it is a hormone, the function is rather slow. Therefore the pathway is divided into an early primary response and a delayed secondary response.
The early primary response is when the steroid hormone binds to its receptor. This complex activates primary-responce genes, which induced synthesis of a few different proteins in the primary response.
Delayed secondary response: A primary response protein shuts off primary-reponse genes (a type of negative feedback), while another primary response protein turns on secondary repsonse genes, which induce synthesis of different secondary-response porteins.
Describe the early primary response of steroid hormones
The steroid hormone binds to the steroid hormone receptor, which activates primary-response genes. This induces synthesis of different primary response proteins
Describe the delayed secondary response
An early primary-response protein shuts of the primary-respones genes, and another early primary-response protein activates secondary response genes, which induces synthesis of secondary response proteins
Name three types of cell-surface receptors
Ion-channel-linked
G-protein linked
Enzyme-linked
Describe ion-channel linked receptors
When the signal molecule (ligand) binds to the receptor, the channel is opened to allow ions to flow through
Describe enzyme-linked receptors
When the signal molecule binds to the receptor, the intracellular domain of the receptor is activated, which activates an enzyme that is associated with the receptor
Describe G protein-linked receptors
The signal molecule bonds to the transmembrane receptor. The G-protein consists of three subunits: alfa, beta and gamma. Upon binding of the ligand, the intracellular part of the receptor activates the G-protein, and GDP is transformed to GTP. The alpha subunit activates the target protein. After this, the GTP will be hydrolysed to GDP, and the alpha subunit dissociates from the target protein, and reassembles with the beta-gamma complex.
Describe the effects of adenylyl cyclase activation (G-protein)
The target protein (adenylyl cyclase) activates cyclic AMP from ATP. Cyclic AMP then binds to protein kinase A (PKA) and activates PKA. Activated PKA translocates to the nucleus, where it activates CREB. The activated CREB then binds CBP (CREB binding protein) on the CREB-binding element on DNA, which mediates transcription of the target gene, which is then translated to the target protein.
Describe the effects of phospholipase C-beta activation (G-protein)
The activation of phospholipase C-beta activates PI-4,5-biphosphate. Activation of PI-4,5-biphosphate triggers it dissociation into diacylglycerol and inositol 1,4,5-triphosphate. Inositol 1,4,5-triphosphate binds to a IP3-gated Ca2+ release channel in the endoplasmic reticulum, which releases Ca2+ from the endoplasmic reticulum. This Ca2+ binds to protein kinase C together with diacylglycerol (DAG), which activates protein kinase C
