VL (Salim Seyfried) Flashcards
Molecular mechanisms of inductive interactions between cells
- Contact-dependent
–> Many signaling pathways e.g: Notch - Paracrine
–> Many signaling pathways & Hormones - Synaptic
- Endocrine
–>Hormones
Cell SIgnaling
* Receiving cell that can respond to an inducing singal is considered competent (e.g. direct interaction; receptor expression)
* Receptor protein provides cell with competence to respond to signaling molecule
* Compentence may be acquired during development by the expression of receptors or formation of gap junctions.
Activation mechanism of
receptor tyrosine kinases
- intracellular tyr kinase domain
- signaling molecule → activates tyr kinases → join receptors →
activation by cross-phosphorylation
Schematic of a signal transduction process
Mechanisms of desensitization to extracellular signals
Pattern formation by morphogen
signaling: The French flag model
- cells can acquire and identity based on positional information; one mechanism by which this is achieved involves morphogens
- morphogens (at different threshold-c)
- diffuse over several cell diamters
- induce different cell fates
Example of a morphogene signaling pathway: WNT pathway
Wnt:
* receptor: frizzled, LRP6
* Wnt absent
–> no complex (frizzled, LRP6, dishevelled)
–> active intracellular complex degrades beta-catenin o repressor complex → no Wnt-transcription
* Wnt present
–> complex formation (frizzled, LRP6, dishevelled, Wnt)
→LRP6 phosphorylation
→degradation box-recruitment to membrane
→dishevelled phosphorylated
→degradation box inactivation
→higher c(beta-catenin) = transcriptional activator
→ nucleus diffusion
→Wnt target genes activated
Hedgehog signaling pathway:
- receptor: patched, smoothened (endosomal vesicles)
- without hedgehog signal
–> patched supresses smoothened → no signaling
–> MT-associated proteins (Costal2, Fused, large Ci (cubitus interruptus)
Roles of WNT signaling
- carcinogenesis
- tissue regeneration in adult bone marrow, skin, intestine
- embryonic development (body axis patterning, cell fate specification, cell proliferation, cell migration)
- processes are necessary for proper formation of important tissues including bone, heart, muscle
Transforming growth factor (TGFβ) signaling:
- Co-Smad4 (role in bone morphorphogenetic pathway BMP)
Notch lateral inhibition
- function: defining cell fate in an equivalence field of cells
- notch activated →1 cell in equivalence field has become delta-expressing cell → other cells (notch-expressing) surround delta- expressing cell
Examples of Notch activity during development:
angiogenesis (left): phys. process through which new blood vessels form from preexisting vessels
somitogenesis (right): somites (=bilaterally paired blocks of paraxial mesoderm that form along anterior-posterior embryo axis) formation
- Tip cells
–> High levels of Delta-like 4, low levels of Notch (Jag1) o Coexpression: VEGFR2
–> grows into direction of VEGF-A - stalk cell
–> low levels of Delta-like 4, high levels of Jag1 → notch lateral inhibition defines differences of tip cell, stalk cell - 2-3 somites form per hour
- Notch/delta-signaling for boundary
formation
Hormone biology
- greek: horman = “to set in motion, urge on”
definition
= chem. substance
* produced in body
* controls/regulates activity of cells/organs
* many are secreted by special endocrine glands and circulate within the circulation/body fluids
Hormone biology
* carried via blood flow → target cells
* elicit effects at low c (10-9 – 10-12 M)
* activity has to be terminated (degradation/excretion via kidney)
Autocrine, paracrine and endocrine signaling
Modes of chemical
communication between animal cells
Neuroendocrine siganling
Control and effector hormones
control hormones (= glandotrope hormones)
* only produced in hypothalamus, pituitary gland (frontal lobe)
* control activity of other hormone glands
effector hormones
* control activity of target organs
* feedback effects on control-hormone producing endocrine glands
The Hypothalamus/pituitary gland axis
- neg. Feedback to prevent Hormone production
Hormones of the neural pituitary gland:
- Neural pituitary
–> In contact with neurosecretory cells with extensions o Interaction neurosecretory cells + capillary network = neurohaemal organ
–> Inhibiting, releasing hormones released into blood
stream - Effector hormones (ADH, Oxytocin) produced by neurosecretory
cells - ADH
–> Central nervous system
–> e.g. blood pressure drop
–> increased integration of aquaporins in kidney →increased blood volume/ pressure - Releasing, inhibiting hormones from neurosecretory cells sensed by endocrine cell
The thyroid gland
- follicle structure
- epithelial cells surround gland
- glands with colloid (+ matrix; with unprocessed, thyroid hormones)
The Thyroid gland hormone system
Hormonal regulation of blood calcium levels:
* Parathormone increases plasmacalcium; produced by parathyroid gland
* high plasmacalcium → neg. feedback on parathyroid gland
* to low c(Ca2+) activate parathormone
Islands of Langerhans/Pancreas:
- Duodenum-associated
- alpha/beta cells in endocrine cells
- Glucagon increases blood-sugar levels
Islands of Langerhans/Pancreas
Beta cell activation by glucose
- High blood sugar levels
- Glucose uptake in beta cells via carrier
→oxidation (glucose broken down)
→higher ATP
→block potassium lack channel (→membrane resting potential)
→depolarisation of membrane (→+-charged)
→voltage-gated calcium channel open
→influx
→increase
→golgi activated
→insulin transported via granula
→secreted
→act on target tissue
→reduced blood sugar levels
ignal transduction mechanisms:
direct effects
* movement of membrane-passable hormone (e.g. steroid hormone) into cell o hormone binding to intra-cellular hormone receptor
* translocation of hormone-receptor complexes into nucleus
→gene activation
Indirect effects
* Hormone binding (first messenger) to membrane receptor o Synthesis of intra-cellular second messenger
→induced phys. hormone effect
* Rapid, short term responses
