Komunikasi sel

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

Komunikasi sel Sel berkomunikasi dengan melepas pembawa pesan (mesenjer)

Lintasan transduksi sinyal Sinyal kimia dikonversi dari satu tipe sinyal menjadi sinyal lain untuk menghasilkan molecular response. All organisms require signaling pathways to live. Huruf mewaliki senyawa kimia atau protein. Tanda panah menunjukkan langkah enzimatik. ABCDEFG

Sel hewan dan sel tumbuhan komunikasi dengan kontak langsung, memiliki cell junctions yang secara langsung menghubungkan sitoplasma dengan sel sebelahnya Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

Pada signaling lokal pada sel hewan, dapat berkomunikasi melalui interaksi antara molekul2 yang menonjol dari permukaan sel Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Cara kerja cell-cell signaling 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).

diffuses across synapse In other cases, animal cells communicate using local regulators (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotran-smitter molecules into a synapse, stimulating the target cell. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse is stimulated Local signaling

Long-distance signaling In long-distance signaling both plants and animals use hormones Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Long-distance signaling Blood vessel Target cell Endocrine cell

Jalur lintasan bersifat inter-linked Signalling pathway Genetic network STIMULUS Metabolic pathway

metabolic pathways 1993 Boehringer Mannheim GmbH - Biochemica

Proses percakapan seluler Terdiri dari 3 tahapan Penerimaan Transduksi Respon EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Transduction 2 Response 3 Reception 1

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

Steroid hormones Bind to intracellular receptors Figure 11.6 1 2 3 4 5 (testosterone) EXTRACELLULAR FLUID Receptor protein DNA mRNA NUCLEUS CYTOPLASM Plasma membrane Hormone- receptor complex New protein Figure 11.6 1 The steroid hormone testosterone passes through the plasma membrane. The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5 Testosterone binds to a receptor protein in the cytoplasm, activating it. 2 The hormone- receptor complex enters the nucleus and binds to specific genes. 3

Receptors in the Plasma Membrane Terdapat tiga tipe reseptor menbran G-protein-linked Tyrosine kinases Ion channel

G-protein-linked receptors Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated Receptor Signal molecule Inctivate Segment that interacts with G proteins GDP GTP P i Signal-binding site Figure 11.7

Receptor tyrosine kinases Signal molecule Signal-binding sit CYTOPLASM Tyrosines Signal molecule Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated 6 ATP 6 ADP

Ion channel receptors Figure 11.7 Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Figure 11.7 Gate closed Ions

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

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 Active protein kinase 1 2 3 Inactive protein kinase Cellular response Receptor P ATP ADP PP Activated relay molecule i Phosphorylation cascade P  A relay molecule activates protein kinase 1. Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 2 then catalyzes the phos- phorylation (and activation) of protein kinase 3. Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 4 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 5

Molekul kecil dan ion sebagai Second Messengers Kecil, nonprotein, molekul yang larut dalam air atau berupa ions Cyclic AMP (cAMP) terbuat dari ATP O –O N O P OH CH2 NH2 ATP Ch2 H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i

G-proteins Memicu pembentukan cAMP, yang kemudian berlaku sebagai second messenger dalam lintasan seluler ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein First messenger (signal molecule such as epinephrine) Figure 11.10

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 FLUID Nucleus CYTOSOL Key Plasma membrane ATP Ca2+ pump Endoplasmic reticulum (ER) Nucleus Mitochondrion Key High [Ca2+] Low [Ca2+]

IP3 quickly diffuses through the cytosol and binds to an IP3– 2 1 IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. 4 The calcium ions activate the next protein in one or more signaling pathways. 6 Calcium ions flow out of the ER (down their con- centration gradient), raising the Ca2+ level in the cytosol. 5 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Various proteins activated Endoplasmic reticulum (ER) Phospholipase C PIP2 IP3 (second messenger) DAG Cellular response GTP Ca2+ (second messenger) IP3-gated calcium channel

Respon sitoplasmik dan nuklear Cell signaling menyebabkan regulasi cytoplasmic activities atau transcription Dalam sitoplasma Jalur signaling mengatur aktivitas seluler yang bervariasi

Respon sitoplasmik Figure 11.13 Glucose-1-phosphate (108 molecules) Glycogen Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Active phosphorylase kinase (105) Inactive phosphorylase kinase Inactive protein kinase A Active protein kinase A (104) ATP Cyclic AMP (104) Active adenylyl cyclase (102) Inactive adenylyl cyclase Inactive G protein Active G protein (102 molecules) Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Response Reception Respon sitoplasmik Figure 11.13

Lintasan lain Mengatur gen dengan mengaktifkan faktor transkripsi yang meng-on dan of-kan gen Reception Transduction Response mRNA NUCLEUS Gene P Active transcription factor Inactive DNA Phosphorylation cascade CYTOPLASM Receptor Growth factor

Jalur signal dengan banyak tahap Dapat memperbesar sinyal dan berpengaruh terhadap kekhususan respon Tiap protein dalam jalur signaling: Mengamplifikasi sinyal dengan mengaktifkan banyak copy dari komponen selanjutnya dalam jalur Kombinasi protein yang berbeda di dalam sel Memberikan kespesifikan yang baik pada sel dalam sinyal yang dideteksi maupun rsepon yang diakibatkan

Berhentinya sinyal Respon sinyal berhenti dengan cepat Dengan lepasnya ikatan ligan