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L25 Cell Signalling ("The physiological way"
classify hormones…
L25 Cell Signalling
"The physiological way"
- classify hormones by site of synth & action
- focus on how far apart the hormone and its Rs is
Contact-dependent
- this signalling reqs (c)s to be in direct memb-memb contact
Juxtacrine
- c respond to sig present on surface of another c
- reqs phys conact between the 2 (c)s
- seen in apoptosis or (c) death where immune (c)s kill infected (eg virus) or 'tumour' cells or during the phagocytosis of dead (c)s eg removal of dead (c)s by macrophages
~ Fas ligand is expressed in the NKC
Paracrine
- signalling (c) synth & releases the hormone
- the target (c) in close proximity (or even adjacent)
- depends on local mediators tht are released into the extra(c)llar space & act on neighbouring (C)s
Synaptic
- performed by neurons tht transmit sigs electrically along their axons & release ntms @ synapses
Endocrine
- hormone synthed & released into bld by the cells of the endocrine gland [endocrine (c)]
- distant target (c)s have spec Rs tht bind the hormone
- the target c : situated a long distance from the source of hormone
- example: insulin production by islets cels of the pancreas
- huge array of hormones= massive effect of many diff target cs
-
Autocrine
- target c IS the one tht produces the hormone often confined to pathologic diseases
- examples:
~ tumour (c) prod a hormone tht promotes its own grwth & grwth of other surrounding cs
~ heart muscle c is stretched mechanically & then releases hormones tht promotes its own gwth
- a hormone may act in any combo
~ eg: adrenaline acts paracrine (as a ntm) but also acts as endocrine (released into bld) & has an effect on distant tg cs
Cell Comm network
No (c) lives in isolation
- survival depends on elaborate comm network [to occur between (C)S]
- (c) adjacent to 1 another comm thru direct c-c contact
- BUT other forms of comm cover larger distances ∴ need extra(c) signalling molecs
~ molecs tht are outside of the (c) tht provide a signal to that target (c)
- the diff combo of these signals are telling these cells to do diff things
~ survive, grow+divide, diffe., apoptosis
~ absence of sigs= smtms tell (c) to undergo apopsotit= (C) death
Signal transduction
- signal molec (outside of the c) binds to Rs prot and then activates intra(c)ullar sig molecs which alters target prots creating a response
- smtms the Rs in the CM, cytosol or even in nuc
Effector prots
- intra(c) signalling prots bring abt a response to the effector prots
- 3 difff responses [what is happening in the cell]
- metabolic ezm → altered metabolism
- Trc regulatory prot → altered gene exp
- cytoskeletal prot → altered (c) shape or mvt
Define Hormones & Rs
Hormones
- = chemical messengers tht coordinate the activities of diff (c)s in an organism
- an alternative to contact for (C)-(C) communication [for larger distances]
- a diverse grp of chemical types
- integral to many biological processes
- Growth factors: similar to hormones (may be prod by a # of diff cells)
Cell A & Cell B
Chemical diversity of hormones is large
- throxine
- testosterone
- epinephrine/adrenaline, iterleukin & insulin [controlling glucose lvls in body]
- for cell signalling, chem sts of molecs are irrelevant, they are simply the RIGHT SHAPE for binding by non-cov interactions w/ great specificity
Receptor
- a memb-bound or soluble prot or prot complex, which exerts a physiological effect (intrinsic effect) after binding its natural ligand.
~ brings abt (C)ullar response in target cell, this occurs when binding
- ligand= a molec tht forms a complex w/ another bimolec & exert a biological effect
= a Multidomain Prot consisting of:
- a hormone binding domain
~ must have this! - essential
~ specifies which hormone binds [the right shape for the hormone to bind]
~ extracellular
- signal-transduction domain
~ essential!
~ the exact biochemistry of this region varies w/ Rs type
~intra(c)ullar in cytoplasm
- transmembrane domain
~ in MOST but NOT ALL
~ part of the prot in the PM
In general:
- Rs are ALWAYS prots
- Rs & hormone bind specifically
- Presence of a Rs allows a cell to respond to a hormone
~ no Rs = no response [bc cant bind tht hormone]
Rs can be Cell-surface or intracellular
- (c)-surface
~ on PM
- intracellular Rs
~ found in nuc
~ here the hormone can cross the PM & cross the nuclear memb
Rs bind spec Hormones (Ligands)
Typical ligands are:
- Small ions:
~ ferric ion: bacterial ferric Rs
- Organic molec:
~ adrenaline: epinephrine Rs
- Polysaccarides
~ heparin: fibroblast growth factor [heparin & its Rs
- Peptides
~ Insulin: Insulin Rs
- Prots
~ vascular endothelial growth factor: VEGF Rs
Classification of hormones by CHEMICAL props
- is it water-sol or not?
- is the hormone "lge" or "sml"
Small lipophilic
- not H2O sol but lipid-sol
- transported in bld bound to carrier prots
- can diffuse thru mems bc sml & lipid-sol
- can have both nuclear & cytosolic Rs
- e.g. steroid hormones (corticoids, oestrogen)
hydrophilic
- water-sol
- not able to diffuse thru membs
- have Rs ON the membs
- a diverse grp
- eg polypeptides (insulin) or sml charged molecs (adrenaline)
Large lipophilic
- too large to diffuse across membs
- have Rs ON the memb
- e.g. prostaglandins [contraction & relaxation of muscle & more]
7 Steps essential for efficient & spec info
- general scheme for comm by extra(c)llar sigs
- Synthesis of hormone
- hormone must be prof by a (c)
- (this synth may be a regulated process -> only made when needed)
- e.g. for insulin: occurs in pancreas (islets of langerhans)
~ insulin = prot, ∴ reqs ⇈d prot synth
~... but not all hormones are prots
- Release of the hormone
- after synth, the h must leave (c) tht made it (release may be regd)
- e.g. for insulin: when glucose lvls are high
- Transport to target (C)
- (a t (c) is able to respond to the h)
- after release the h must get to where it is supposed to be acting
- e.g. for insulin, transported in bld to sites of action in tc: muscle, heart, adipose tissue
- Detection of hormone by tc
- reqs SPEC binding of h by (c) - Rs of the tc
- Rs = prots tht bind h: most common examples are those on the (c) surface
~ie. the Rs is a transmemb prot
- e.g. for insulin
~ insulin Rs: found on plasma membs of (c) in muscle, heart, adipose tisue
~ ie. TCs have the (insulin) Rs
- Transduction of the signal frm the Rs
- this MOVES the sig from OUTSIDE -> INSIDE
- ∴ extracell to intracellular - possibly even to the nuc of the TC
- TC response
- Metabolism
- Growth
- Differentiation
- e.g. for insulin, ⇈s glucose uptake, alteration in metb, some (C)s ⇈size,#
- quick/slow, transient/sustained . respose
- Termination of the sig
- if the sig is not stopped then the response does not stop
The RESPONSE of the TC may involve
- changes in ezm act.
~ the modification of existing ezms is a RAPID RESPONSE [ via phos or dephos to activate or deactivate tht molec]
~ ie. seconds to minutes
- changes in exp of prots
~ by regu of gene Trc etc
~ this is SLOWER, but potentially longer lasting effects
~ bc once tht prot has been expressed: it can work in the (c) depending on how stable tht prot is
-
Function of a hormone is to bind to a spec RECEPTOR
- the RESPONSE of (c) is dictated by presence of a spec Rs
- diff (C)s may have the same Rs
- one (C) may have many diff Rs
They can respond to same stim BUT may invoke a diff biological response
The same chem messenger can prod many diff ∆s
- eg: ace coa: same chem mess can prod many diff ∆s in TCs
can bring abt effecr in:
- acetylcholine:
- heart pacemaker (c): ⇊d rate of firing
- salivary gland (c): secretion
- sk muscle (c): contraction
- ⇊s rate & force of muscle contractions in :<3: muscle (c)s
- stimulates muscle contraction in sk muscle
~ the Rs prots on sk muscle (c)s differ from those on :<3: muscle (c)s
- Stimulates secretion of digestive ezms act. in salivary gland (c)s
~ the Rs prots on :<3: muscle (c) & salivary gland (C)s are identical
- smtm diff (c) can have diff Rs but same response
- smtm same h but diff response
one (c) can have many diff Rs
- lots of diff Rs binding diff hormones
- ∴ tht particular (c) can respond to lots of diff stimuli
- there is the possibility to respond to many diff stimuli
~ smtm w/ same consequences
~ smtm w/ diff consequences
Learning Outcomes
- Understand tht (C) survival depeends on a complex comm network
- Define terms "hormones" & "receptors"
- Classify hormones by
~ site of synth & action (the "physiological way")
~ chem props (the "biochem way")
- Define 7 steps essential for efficient & specific info transfer