cell surface, autocrine, paracrine & intracellular signalling

1.  Cell to Cell Signaling: Hormones and
Receptors Cell Signaling
 Fact - No cell lives in isolation
 Bacteria
 Fossil records – sophisticated unicellular organisms
resembling present day bacteria – on earth 3.5b years
ago but
 Apparently – 2.5b years – for first multi-cellular
organisms to appear
 Why was multi-cellularity so slow to evolve?
Answer is X
 Signaling Mechanism

2.  Cells in multi-cellular organism need to communicate with
one another in order to:
 Regulate their development and organization
into tissues
 Control their growth and
 Coordinate their functions
 Therefore in all multi-cellular organisms,
survival depends on elaborate inter-cellular
communication net work
 Hundreds of kinds of signaling molecules
including proteins, small peptides, amino acids,
nucleotides, steroids, retinoid, fatty acid
derivatives and even dissolved gases such as
nitric oxide and carbon monoxide
 Most of these molecules i.e. signaling
molecules are secreted from signaling cells by
exocytosis

3.  Others are released by diffusion through plasma
membrane
 While some remain tightly bound to cell surface
and influence only cells that contact the signaling
cell
Fig. 15.1 Alberts 3rd Ed
Fig. 15.7 Alberts 3rd Ed
 Extra Cellular Signaling Molecules are Recognized
by Specific Receptors on OR in Target Cells
Fig. 15.2 Alberts 3rd Ed
 Act at very low concentrations - typically ≤10 -8 M
 Receptors that recognize them with high affinity
(affinity constant ka ≥108 M

7.  Secreted Molecules Mediate Three Forms of
Signaling: Paracrine, Synaptic and
Endocrine
Fig. 15.3 Alberts 3rd Ed
 Endocrine cells and nerve cells work together to
coordinate the diverse activities of billions of cells in
higher animals
 Endocrine signaling depends on diffusion and blood
flow – so it is relatively slow and takes minutes for
hormones to reach to target cells after secretion
 Specificity of signaling entirely depends on
 Chemistry of signal
 Receptor of target cell

9. Fig 15.4A Alberts 3rd Ed
 Nerve cells, by contrast, can achieve much greater speed and
precision
 Transmit signal over long distances by means of electrical
impulses at rates up to 100 meters / sec
 At nerve terminal electrical impulse converts into chemical
signal only at the time of release of neurotransmitters
Fig 15.4B Alberts 3rd Ed
 Hormones diluted in the blood stream and interstitial fluid,
low cones < 10 -8 M
 Neurotransmitters: acetylcholine 5x10-4 M- receptors with
low affinity – do not response to low concentration of
neurotransmitters that reached them by diffusion from
neighboring synapses

12.  Neurotransmitters quickly removed either by:
 Specific hydrolytic enzymes
 Specific membrane transport proteins that pump the
neurotransmitters back into nerve terminal or
neighboring glial cells
 This rapid removal ensured not only spatial precision of the
signal but also temporal precision
 A brief pulse of neurotransmitter release evokes a prompt and
brief response
 So that timing of signal can be faithfully relayed from cell to
cell
Fig 12.4 Alberts 2nd Ed

14.  Signaling Molecules:
Table 12.1 Alberts 2nd Ed
Table 24.3 Zubay
 Autocrine Signaling can Coordinate
Decisions by Groups of Identical Cells:
 One cell type to influence another:
 Development and differentiation “community effect”
in early development
 Eicosanoids in mature mammals often act in autocrine
mode
Fig. 15.5 Alberts 3rd Ed
Fig. 15.6 Alberts 3rd Ed

18. Human chorionic Gonadotropin (hCG)

19. Gonadotropin releasing hormone/factor (Gn-RH)

26.  Each Cell is Programmed to Respond to
Specific Combination of Signaling
Molecules:
 Any given cell in multi-cellular organism is exposed to
many rather hundreds of different signals from its
environment
 These signals can be:
 Soluble / bound to extra cellular matrix
OR
 Bound to the surface of neighboring cell and
can act in many millions of possible
combinations
 The cell must respond to this Babel selectively
according
 to its specific character- acquired through progressive
cell specialization in the course of development

27.  Thus a cell may be programmed to respond to
 One set of signals by differentiating
 Another set by proliferating
 Yet another by carrying out some specialized function
 Most cells in higher animals, moreover, are programmed to
depend on a specific sets of signals simply for survival
 When deprived of a appropriate signals (in a culture dish, for
example) a cell will activate a suicide program and kill itself –
a process called programmed cell death
Fig. 15.8 Alberts 3rd Ed
 Different types of cells require different sets of survival signals
and so are restricted to different environments in the body
 Because signaling molecules generally act in combinations, an
animal can control the behaviors of its cell in highly specific
ways using a limited diversity of such molecules: hundreds of
such signals can be used in millions of combinations

29.  Different Cells can Respond Differently to
the Same Chemical Signal:
 Specific way a cell reacts to its environment varies first
according to:
 Set of receptor proteins cell possesses which it
is tuned to detect a particular subset of the
available signals and second according to
 Intracellular machinery by which cells integrates
and interprets the receiving information that it
receives
 Thus a signaling molecule often has different effects
on different target cells
Fig. 15.9, Alberts 3rd Ed

31.  Some Cellular Responses to Chemical
Signal Rapid and Transient while other
are Slow and Long Lasting:
 Rapid and Transient
 In coordinating the responses of cells to changes in
an animals environment, chemical signal generally
induce rapid and transient responses. For example:
 An increase in blood glucose levels stimulate
endocrine cells in pancreas to secret insulin
into blood
 Within a minutes resulting in insulin
concentration stimulates fat and muscle cells
to take up more glucose
 As a result blood glucose levels

32.  There are three parts to response – non of which requires
new protein synthesis:
 In pancreas glucose levels trigger the exocytotic
release of stored insulin
 In fat and muscle cells, extra membrane bound
glucose transport proteins are stored in intra-
cellular vesicles and the levels of insulin cause
these proteins to be added by exocytosis to the
plasma membrane – increase the rate of glucose
uptake
 This causes blood glucose levels to hence the
rate of insulin secretion

33.  Since the extra glucose carriers are rapidly removed
from the cell surface by endocytosis and returned to
the intracellular pool, when insulin levels , the rate of
glucose uptake by fat and muscle cells return to its
previous level
 In this way insulin helps to maintain a relatively
constant blood glucose concentration
 Neurotransmitters elicit even more rapid responses than
hormones do. For exasmple:
 Skeletal muscle cells contract and relay again within
milliseconds in response to acetylcholine
 Slow and Long Lasting Effect
 Estradiol – a female sex hormone – secreted in large
amounts by cells in ovary around time of puberty

34. • It induces changes in wide variety of cells in different
parts of the body
• Changes that eventually lead to the development of
secondary female characteristics such as breast
enlargement
 Thyroid Hormone – A tenfold increase in thyroid
hormone levels in the blood of a tadpole, includes the
dramatic and irreversible changes that result in its
transformation into frog
Fig. 12.6 Alberts 2nd Ed

36.  Synthesis, Release and Degradation of
Hormones are Regulated:
 Because of their potent effects, hormones and
neurotransmitters must be carefully regulated
 As we discussed earlier that the release and
degradation of some signaling compounds are
regulated to:
 Produce rapid, short-term effects
 Other to produce slower acting but longer –
lasting effects
 In some cases, complex regulatory networks
coordinate the levels of hormones whose effects
are interconnected