TRANSDUKSI, SINAP

DAN
NEUROTRANSMITER
AFRIWARDI
 Sistem tubuh
• Identik dengan “pemerintahan nyata”
• Terdiri : Subsistem
• Penghubung dan kordinasi antara subsistem
• Pesan dikirim atau diterjemahkan
Komunikasi sel
Sel berkomunikasi
dengan melepas
pembawa pesan
(mesenjer)
Komunikasi interseluler
 KEPERLUAN KOMUNIKASI
• FUNGSI PENGONTROLAN ( SARAF DAN
HORMON)
– METABOLISME
– PERTUMBUHAN
– DIFERENSIASI JARINGAN
– SINTESA DAN SEKRESI PROTEIN
– KOMPOSISI CAIRAN
– DLL
Sel komunikasi essential bagi organisme multiseluler
Sinyal eksternal diubah menjadi respon di dalam sel

Signal transduction pathways/jalur transduksi sinyal

Sinyal pada permukaan sel dikonversi menjadi respon
seluler spesifik melalui serangkaian langkah
Pensinyalan ini mirip baik pada microbes (yeast) dan
mamalia, tumbuhan mekanisme pensinyalan telah
berkembang dengan baik sebelum mahluk multiseluler
muncul di bumi
 Lintasan transduksi sinyal
• Sinyal kimia dikonversi dari satu tipe sinyal menjadi sinyal lain untuk
menghasilkan molecular response.
• Merubah energi jadi energi lain : fisik jadi listrik, kimia jadi listrik, dll
• All organisms require signaling pathways to live.
• Pesan berantai

ABCDEFG
• Huruf mewaliki senyawa kimia atau protein.
Tanda panah menunjukkan langkah enzimatik.
 KOMUNIKASI SEL
• MOLEKUL SIGNAL EKSTRA SELULER (LIGAN)
– HIDROFILIK : ASAM AMINO, PEPTIDA,
ASETILKOLIN, DLL
– HIDROFOBIK : STEROID, RETINOL, TIROKSIN
• RESEPTOR
– PERMUKAAN MEMBRAN SEL
– SITOPLASMA
– INTI SEL
 JARAK KOMUNIKASI
• DIRI SENDIRI : OTOKRIN
– MERESPON MOLEKUL YANG DIHASILKANNYA
– SEL TUMOR
• TETANGGA : JUKTAKRIN
– KONTAK LANGSUNG
– TONJOLAN
• JARAK PENDEK : PARAKRIN
• JARAK JAUH : ENDOKRIN
 KONTAK LANGSUNG

Plasma membranes

Gap junctions Plasmodesmata

between animal cells between plant cells

Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.
 KONTAK TONJOLAN

Cell-cell recognition. Two cells in an animal may communicate by interaction

between molecules protruding from their surfaces.
 TAHAP KOMUNIKASI LIGAN
• SINTESA
• PENGLEPASAN MOLEKUL SIGNAL(LIGAN)
• TRANSPORTASI KE SEL TARGET
• IKATAN MOLEKUL SIGNAL DENGAN RESEPTOR
• PERUBAHAN FUNGSI SPESIFIK : METABOLISME
ATAU PERKEMBANGAN
• PENGLEPASAN IKATAN LIGAN DENGAN
RESEPTOR  RESPON SELULER BERHENTI
 TAHAP KOMUNIKASI LIGAN
Direct
Pensinyalan kimiawi jarak dekat
• Pensinyalan parakrin. Molekul sinyal dikeluarkan oleh sebuah sel dan
bekerja pada sel target di dekatnya. Molekul pengatur lokal dilepas
ke dalam fluida ekstraseluler
• Pensinyalan sinaptik. Sel saraf melepaskan molekul neurotransmiter
ke dalam sinapsis.
Jarak yang lebih jauh
• Pensinyalan hormonal. Sel endokrin mensekresi hormon ke dalam
cairan tubuh (darah).
 KOMUNIKASI JARAK PENDEK
Local signaling

Target cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter

Neurotransmitter
Secretory
diffuses across
vesicle
synapse

Local regulator
diffuses through
extracellular fluid Target cell
is stimulated

(b) Synaptic signaling. A nerve cell releases neurotran-smitter

(a) Paracrine signaling. A secreting cell acts on nearby molecules into a synapse, stimulating the
target cells by discharging molecules of a local regulator (a target cell.
growth factor, for example) into the extracellular fluid.
 KOMUNIKASI JARAK JAUH
Long-distance signaling

Endocrine cell Blood

vessel

Hormone travels
in bloodstream
(c) Hormonal signaling. Specialized to target cells
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
Target
cell
 Proses percakapan seluler
Terdiri dari 3 tahapan
1.Penerimaan
2.Transduksi
3.Respon
EXTRACELLULAR CYTOPLASM
FLUID Plasma membrane

2 Transduction 3 Response
1 Reception

Receptor

Activation
of cellular
response
Relay molecules in a signal transduction pathway

Signal
molecule
 Reception/Penerimaan: pendeteksian sinyal yang
datang dari luar sel oleh sel target
 Pengikatan molekul sinyal mengubah protein reseptor
mengawali proses transduksi
 reseptor bersifat sangat spesifik
 Intracellular receptors cytoplasmic or nuclear proteins
Molekul sinyal yang menggunakan reseptor ini adalah yang
kecil atau hydrophobic dan dapat langsung melewati
plasma membran
 Reseptor pada plasma membran

 Sinyal yang ditransduksi memicu respon selular spesifik

Receptors in the Plasma Membrane

• Terdapat tiga tipe reseptor menbran

– G-protein-linked
– Tyrosine kinases
– Ion channel
 G-protein-linked receptors
Signal-binding site

Segment that
interacts with
G proteins

G-protein-linked Activated Inctivate

Plasma Membrane Signal molecule
Receptor Receptor enzyme

GDP
G-protein GDP GTP
CYTOPLASM (inactive) Enzyme

Activated
enzyme

GTP
GDP
Pi

Cellular response
Figure 11.7
Receptor tyrosine kinases
Signal Signal-binding sit
molecule
Signal
Helix in the molecule
Membrane

Tyr Tyr
Tyr Tyr Tyr Tyr
Tyrosines Tyr Tyr
Tyr Tyr Tyr Tyr
Tyr Tyr
Tyr Tyr Tyr Tyr

Receptor tyrosine
CYTOPLASM kinase proteins Dimer
(inactive monomers)

Activated
relay proteins

Cellular
Tyr Tyr P Tyr Tyr P P Tyr Tyr P
Tyr P
response 1
Tyr Tyr P Tyr Tyr P P Tyr
Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular
6 ATP 6 ADP
response 2
Activated tyrosine- Fully activated receptor
kinase regions tyrosine-kinase Inactive
(unphosphorylated (phosphorylated relay proteins
dimer) dimer)
 Ion channel receptors
Signal Gate closed Ions
molecule
(ligand)

Ligand-gated Plasma
ion channel receptor Membrane

Gate open

Cellular
response

Gate close

Figure 11.7
• Steroid hormones

– PENERIMAAN (IKATAN LIGAN DG RESEPTOR)

Hormone EXTRACELLULAR
(testosterone) FLUID 1 The steroid
hormone testosterone
passes through the
plasma membrane.
Plasma
Receptor membrane
2 Testosterone binds
protein to a receptor protein
Hormone- in the cytoplasm,
receptor activating it.
complex

3 The hormone-
receptor complex
enters the nucleus
and binds to specific
DNA genes.
mRNA 4 The bound protein
stimulates the
transcription of
NUCLEUS New protein the gene into mRNA.

5 The mRNA is
translated into a
specific protein.
Figure 11.6 CYTOPLASM
 Lintasan transduksi sinyal
• Transduksi: Jalur interaksi molekuler yang menyalurkan sinyal dari
reseptor ke molekul target dalam sel

• Multistep pathways
– Memperbesar sinyal
– Memberikan lebih banyak kesempatan untuk koordinasi dan
regulasi
 Jalur lintasan
Signalling pathway

STIMULUS Genetic
network

Metabolic pathway
 Protein Phosphorylation and
Dephosphorylation
• Banyak jalur sinyal termasuk jalur phosphorylation

Mekanisme utama transduksi sinyal

 Dalam proses ini

 Sejumlah protein kinase menambahkan fosfat
kepada protein kinase lainnya dan
mengaktifkannya
 Enzim fosfatase selanjutnya menghilangkan fosfat
 A phosphorylation cascade
Signal molecule

Receptor Activated relay 1 A relay molecule

molecule activates protein kinase 1.

Inactive
protein kinase 2 Active protein kinase 1
1 Active transfers a phosphate from ATP
protein to an inactive molecule of
kinase protein kinase 2, thus activating
1 this second kinase.
Inactive
protein kinase ATP
2 ADP Active P 3 Active protein kinase 2
protein then catalyzes the phos-
PP kinase phorylation (and activation) of
Pi 2 protein kinase 3.

Inactive
protein kinase ATP
3 ADP Active P 4 Finally, active protein
protein kinase 3 phosphorylates a
5 Enzymes called protein kinase
PP protein (pink) that brings
phosphatases (PP) Pi 3 about the cell’s response to
catalyze the removal of the signal.
the phosphate groups Inactive
from the proteins, protein ATP
making them inactive ADP P
and available for reuse. Active Cellular
protein response
PP
Pi
 Molekul kecil dan ion sebagai Second
Messengers
• Second messengers
– Kecil, nonprotein, molekul yang larut dalam air atau
berupa ions

 Cyclic AMP (cAMP) terbuat dari ATP

NH2 NH2 NH2

N N N
N N N

O O N N N O N N
O N
Adenylyl cyclase Phoshodiesterase
– HO P O CH2
O P O P O P O Ch2
CH2
O O O O O O O
O O
Pyrophosphate P H2O
P Pi O O
OH OH OH OH OH
ATP Cyclic AMP AMP
• G-proteins
– Memicu pembentukan cAMP, yang kemudian berlaku
sebagai second messenger dalam
lintasan seluler First messenger
(signal molecule
such as epinephrine) Adenylyl
G protein cyclase

G-protein-linked GTP
receptor
ATP
cAMP

Protein
kinase A

Figure 11.10 Cellular responses

 Calcium ions and Inositol
Triphosphate (IP3)
• Calsium, saat dikeluarkan ke dalam sitosol
– Bertindak sebagai second messenger dalam berbagai jalur

 Calsium adalah second messenger yang penting

 Karena sel mampu mengatur konsentrasinya dalam
sitosol

 Second messengers seperti inositol triphosphate dan

diacylglycerol (DAG) dapat memicu peningkatan
kalsium di sitosol
EXTRACELLULAR Plasma
FLUID membrane

Ca2+
ATP pump
Mitochondrion

Nucleus

CYTOSOL

Ca2+
pump
Endoplasmic
ATP Ca2+ reticulum (ER)
pump

Key High [Ca2+] Low [Ca2+]

 1 A signal molecule binds 2 Phospholipase C cleaves a 3 DAG functions as
to a receptor, leading to plasma membrane phospholipid a second messenger
activation of phospholipase C. called PIP2 into DAG and IP3. in other pathways.

EXTRA-
Signal molecule
CELLULAR
(first messenger)
FLUID
G protein

DAG
GTP

G-protein-linked PIP2
receptor Phospholipase C
IP3
(second messenger)

IP3-gated
calcium channel

Endoplasmic Various
reticulum (ER) Cellular
Ca2+ proteins
response
activated
Ca2+
(second
messenger)

4 IP3 quickly diffuses through 5 Calcium ions flow out of 6 The calcium ions
the cytosol and binds to an IP3– the ER (down their con- activate the next
gated calcium channel in the ER centration gradient), raising protein in one or more
membrane, causing it to open. the Ca2+ level in the cytosol. signaling pathways.
 Respon sitoplasmik dan nuklear
 Respon:
Cell signaling menyebabkan regulasi cytoplasmic
activities atau transcription

 Dalam sitoplasma
 Jalur signaling mengatur aktivitas seluler yang
bervariasi
 Reception

Binding of epinephrine to G-protein-linked receptor (1 molecule)

Respon sitoplasmik Transduction

Inactive G protein

Active G protein (102 molecules)

Inactive adenylyl cyclase

Active adenylyl cyclase (102)

ATP
Cyclic AMP (104)

Inactive protein kinase A

Active protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

Response
Glycogen
Figure 11.13 Glucose-1-phosphate
(108 molecules)
• Lintasan lain
– Mengatur gen dengan mengaktifkan faktor transkripsi yang
meng-on dan of-kan gen
Growth factor Reception
Receptor

Phosphorylation
cascade
Transduction

CYTOPLASM

Inactive
transcription Active
factor transcription
factor Response
P
DNA
Gene

NUCLEUS mRNA
Bentuk hubungan

- Saraf – saraf : synaps

- saraf –otot : myo-neural junction

Hubungan syaraf-syaraf pada suatu sel syaraf:
Synaps
Hubungan syaraf-syaraf pada suatu sel syaraf
Ujung terminal syaraf
Penyebaran potensial aksi
ke serat syaraf berikutnya

Melalui synaps

Neuro-transmitter
- Asetilkolin
 Synaptic Transmission
Direction of
nerve impulse

• Neurotransmitters are released

Synaptic
when impulse reaches synaptic Axon
vesicles Presynaptic neuron
knob Ca+2 Ca+2

Synaptic knob Cell body or dendrite

of postsynaptic neuron

Mitochondrion

Synaptic
Ca+2 vesicle
Vesicle releasing
neurotransmitter
Axon
membrane
Neurotransmitter
Synaptic cleft

Polarized
membrane
Depolarized
membrane
40
(a)
 Animation:
Chemical Synapse

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41
Penyebaran potensial aksi ke otot:
Myoneural junction
Penyebaran potensial aksi
dari syaraf ke otot:
neuro-muscular transmision

Melalui myo-neural junction

Neuro-transmitter
- Asetilkolin
1. An action potential arrives at the Presynaptic
Action
presynaptic terminal causing voltage Ca2+ terminal ACh
gated Ca2+ channels to open, Presynaptic potential
channel terminal
increasing the Ca2+ permeability of Ca2+
the presynaptic terminal. Acetic
Synaptic acid
1 vesicle
2. Ca2+ enters the presynaptic terminal
and initiates the release of a Synaptic cleft
Choline
neurotransmitter, acetylcholine (ACh),
2
from synaptic vesicles in the
presynaptic terminal.

3. Diffusion of ACh across the synaptic 7

ACh Choline Acetic
cleft and binding of ACh to ACh
receptors on the postsynaptic muscle Na+ acid
fiber membrane causes an increase in ACh
Synaptic
the permeability of ligand-gated Na+ 3 6
5 cleft ACh
channels.
4 receptor
4. The increase in Na+ permeability site
results in depolarization of the Action Receptor Action
postsynaptic membrane; once potential molecule potential
threshold has been reached a Na+
postsynaptic action potential results. Postsynaptic
membrane Acetylcholinesterase
5. Once ACh is released into the synaptic cleft it binds to the receptors for
ACh on the postsynaptic membrane and causes Na+ channels to open. Na+

6. ACh is rapidly broken down in the synaptic cleft by

etylcholinesterase to acetic acid and choline.

7. The choline is reabsorbed by the presynaptic terminal and combined

with acetic acid to form more ACh, which enters synaptic vesicles.
Acetic acid is taken up by many cell types.
 Action
Ca2+ Presynaptic potential
channel terminal
Ca2+

An action potential arrives at the presynaptic terminal causing voltage

gated Ca2+ channels to open, increasing the Ca2+ permeability of
the presynaptic terminal.
 Ca2+ Presynaptic
channel terminal
Ca2+

ACh

Ca2+ enters the presynaptic terminal and initiates the release of a

neurotransmitter, acetylcholine (ACh), from synaptic vesicles in the
presynaptic terminal.
 Synaptic cleft

Na+
ACh

Receptor
Na+ molecule

Diffusion of ACh across the synaptic cleft and binding of ACh to ACh
receptors on the postsynaptic muscle fiber membrane causes an
increase in the permeability of ligand-gated Na+ channels.
 Na+

Action Action
potential Na+ potential

The increase in Na+ permeability results in depolarization of the

postsynaptic membrane; once threshold has been reached a
postsynaptic action potential results.
 ACh

Synaptic ACh
cleft receptor
site

Postsynaptic
membrane
Na+

Once ACh is released into the synaptic cleft it binds to the receptors for
ACh on the postsynaptic membrane and causes Na+ channels to open.
 ACh Choline Acetic
acid
ACh
receptor
site

Acetylcholinesterase

ACh is rapidly broken down in the synaptic cleft by

acetylcholinesterase to acetic acid and choline.
 Presynaptic ACh
terminal
Acetic
Synaptic
acid
vesicle
Choline

ACh Choline

The choline is reabsorbed by the presynaptic terminal and combined

with acetic acid to form more ACh, which enters synaptic vesicles.
 Choline Acetic
acid

Acetic acid is taken up by many cell types.