Life: the Science of Biology

Lecture Notebook to accompany

Sinauer Associates, Inc. MacMillan

Copyright © 2014 Sinauer Associates, Inc. Cover photograph © Alex Mustard/naturepl.com. This document may not be modified or distributed (either electronically or on paper) without the permission of the publisher, with the following exception: Individual users may enter their own notes into this document and may print it for their own personal use. Cell Communication 7 and Multicellularity

(A) Juxtacrine signals bind to adjacent cells. Paracrine signals bind to Target cell receptors on nearby cells.

Receptor Secreting cell

Target cell

Cells without receptors for a Autocrine signals bind to particular signal receptors on the same do not respond cell that secretes them. Not a target cell (no receptors) to that signal.

(B) Circulating signals such as hormones are transported by the circulatory system and bind to receptors on distant cells. Target cell

Circulatory vessel Secreting cell (e.g., a blood vessel)

Target cell

7.1 Chemical Signaling Systems (Page 126)

To add your own notes to any page, use Adobe Reader’s Typewriter feature, accessible via the Typewriter bar at the top of the window. LIFE(Requires The Science Adobe of Biology Reader 10E 8 or later.Sadava Adobe Reader can be downloaded free of charge from the Adobe website: http://get.adobe.com/reader.) Sinauer Associates Morales Studio 2Figure 07.01 Date 04-27-12 © 2014 Sinauer Associates, Inc. Chapter 7 | Cell Communication and Multicellularity 3

1 A signal arrives Signal at a target cell. molecule

2 The signal molecule binds to a Receptor receptor protein in the cell surface or inside the cytoplasm.

3 Signal binding changes the three- dimensional shape (conformation) of the receptor and exposes its active site.

Short-term changes: enzyme activation, cell movement

Inactive Activated signal signal transduction transduction molecule molecule

4 The activated receptor activates a Long-term signal transduction pathway to changes: bring about cellular changes. altered DNA transcription

The receptor has both extracellular (A) and intracellular regions connected Outside by a hydrophobic region. 7.2 A Signal Transduction Pathway (Page 127) of cell The signal (ligand) fits Plasma into the receptor at membrane its extracellular region.

Inside of cell

LIFE The Science of Biology 10E Sadava (B) O NH Sinauer Associates 2 CH3 H C N N Morales Studio 3 N N Figure 07.02 Date 04-25-12

O N N N N O OH CH 3 H H Caffeine Adenosine H H OH OH

The similar structures of caffeine and adenosine allow them both to bind the receptor, but only adenosine triggers signal transduction.

7.3 A Signal and Its Receptor (Page 128)

LIFE The Science of Biology 10E Sadava Photo to come Sinauer Associates Morales Studio Figure 07.03 Date 04-25-12 Chapter 7 | Cell Communication and Multicellularity 4

Outside of cell Nonpolar Transmembrane Polar signal receptor signal Plasma membrane

Receptor

A signal that is polar and/or large cannot diffuse through A nonpolar signal can diffuse directly the plasma membrane. Its across the lipid bilayer of the plasma receptor is embedded in membrane to encounter its receptor the membrane. in the cytoplasm or nucleus. Inside of cell

7.4 Two Locations for Receptors (Page 129)

1 Acetylcholine binds to two of the five Outside AChR subunits, causing the channel of cell to change shape and open. Na+ Acetylcholine (ACh)

Plasma membrane 2 The channel is lined with – – – – negatively – – charged amino – – acids, allowing Na+ to flow into the cell. LIFE The ScienceAcetylcholine of Biology 10E Sadava Sinauer Associatesreceptor (AChR) Morales Studio Figure 07.04 Date 04-25-12 Inside of cell 3 Na+ buildup in cells leads to muscle contraction.

7.5 A Gated Ion Channel (Page 129)

Protein kinase Target protein + ATP protein- P + ADP (altered shape and function)

In-Text Art (Page 129)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.05 Date 04-25-12

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.UN 1 04-25-12 Chapter 7 | Cell Communication and Multicellularity 5

1 The α subunits of 2 A conformational change in the the receptor bind β subunits transmits a signal to the insulin (the signal). cytoplasm that insulin is present.

Insulin

Outside of cell β α α β β α α β

3 The insulin signal activates the receptor’s protein kinase domain in the cytoplasm… P P Phosphate P P P P P P groups 4 …which phosphorylates insulin-response Insulin substrates, triggering receptor P a cascade of chemical responses inside the cell. Insulin-response substrate

Cellular responses Inside of cell

7.6 A Protein Kinase Receptor (Page 130)

(A) (B) (C) LIFE The Science of Biology 10E Sadava 1 Hormone binding to the receptor 2 Part of the activated G protein Sinauer Associates activates the G protein. GTP activates an effector protein that MoralesOutside Studio of cell replaces GDP. causes changes in cell function. Figure 07.06 Date 04-25-12 Signal (hormone)

Activated effector protein

GDP GTP GDP G protein- linked 3 The GTP on the G receptor Inactive Inactive effector Activated protein is hydrolyzed G protein protein G protein to GDP. Cellular responses Inside of cell

7.7 A G Protein-Linked Receptor (Page 130)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.07 Date 04-25-12 Chapter 7 | Cell Communication and Multicellularity 6

Plasma Outside of cell Signal (cortisol) membrane

Inside of cell 2 Cortisol enters the 1 The receptor– cytoplasm and binds Cortisol chaperone to the receptor… receptor complex cannot enter the nucleus. 3 …causing the receptor to change Chaperone shape and release protein the chaperone…

4 …which allows the receptor and the cortisol ligand to enter the nucleus.

DNA

Nucleus Transcription mRNA

7.8 An Intracellular Receptor (Page 131)

(A) Normal cell Receptor activation leads to activation of the G protein, Ras. LIFE The Science of Biology 10E Sadava Sinauer Associates GDP GTP Morales Studio Figure 07.08 Date 04-25-12

Ras Ras Brief stimulation GDP GTP of cell division

After a brief time in the activated Pi state, Ras returns to its inactive form.

(B) Cancer cell Receptor activation leads to activation of Ras, which stays active.

GDP GTP Abnormal Ras

Ras Ras Constant stimulation GDP GTP of cell division

7.9 Signal Transduction and Cancer (Page 132)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.09 Date 04-25-12 Chapter 7 | Cell Communication and Multicellularity 7

Growth factor Outside of cell 1 A growth factor binds its receptor… 2 …which phosphorylates itself. 4 Activated Ras binds and activates Raf.

Ras GDP P P Ras Ras Raf Inside of cell P P Inactive P P P P GTP 5 Activated Raf is a protein Active P kinase that phosphorylates Raf MEK MEK many molecules of MEK. 3 The activated receptor initiates a series of events that allow Ras P MAPK to bind GTP and become activated. MAPK

6 Activated MEK is a protein kinase that phosphorylates many Nucleus molecules of MAP kinase.

P 7 MAP kinase, when activated MAPK by phosphorylation, can enter the nucleus.

Cellular responses (including stimulation of cell division)

7.10 A Protein Kinase Cascade (Page 132)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.10 Date 04-25-12

INVESTIGATINGLIFE 7.11 The Discovery of a Second Messenger

HYPOTHESIS A second messenger mediates between receptor activation at the plasma membrane and enzyme activation in the cytoplasm.

Method Liver 1 Liver tissue is homogenized and separated into plasma membrane and cytoplasm fractions. Cytoplasm contains inactive Membranes glycogen contain phosphorylase epinephrine receptors

2 The hormone epinephrine is added to the membranes and allowed to incubate.

3 The membranes are removed by centrifugation, leaving only the solution in which they were incubated.

4 Drops of membrane-free solution are added to the cytoplasm.

Results Glycogen phosphorylase in the cytoplasm is activated. Outside cell CONCLUSION A soluble second messenger, produced by hormone-activated membranes, is present in the solution and activates enzymes in the cytoplasm. Go to BioPortal for discussion and relevant links for all Adenylyl cyclase INVESTIGATINGLIFE figures. Inside cell

(Page 133) ATP cAMP+ PPi

NH NH Adenine 2 2 C C N C N N C N CH CH HC C N HC C N N N

O O O – O P O P O P O CH2 O O CH2 O – – – O O O HC H H CH HC H H CH Phosphate groups OH OH O P O OH –O

ATP Cyclic AMP (cAMP) 7.12 The Formation of Cyclic AMP (Page 133)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 7.12 Date 04-25-12 Chapter 7 | Cell Communication and Multicellularity 9

Epinephrine

Glycogen phosphorylase Glycogen glucose In-Text Art (Page 133)

Receptor 1 Signaling pathway 1 Second messenger Receptor 2 Signaling pathway 2

In-Text Art (Page 134)

Phospholipase C PIP2 IP3 + DAG In membrane Released to In membrane cytoplasm

In-Text Art (Page 134)

Outside of cell LIFE The Science of Biology 10E Sadava 1 The receptor binds the hormone. Sinauer Associates MoralesHormone Studio 2+ Phospholipase C 5 DAG and Ca activate Figure 07.UN 1 04-25-12 protein kinase C (PKC). Receptor PIP2 DAG LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio PKC Figure 07.UN 2 04-25-12 P P P 3 The activated enzyme GTP Cellular Li+ blocks produces the second Li+ blocks messengers DAG and responses IP3 from PIP2. 2 The activated G protein P subunit dissociates and P LIFE The Science of Biology 10E Sadava IP3 activates phospholipase C. P 6 PKC phosphorylates Sinauer Associates enzymes and other Morales Studio Ca2+ proteins. Figure 07.UN 3 04-25-12 P Lumen of smooth P P endoplasmic reticulum 2+ 4 IP3 opens Ca channels, leading to an increase in 2+ Inside of cell cytosolic Ca .

High Ca2+

7.13 The IP3/DAG Second-Messenger System (Page 135)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 7.13 Date 04-25-12 Chapter 7 | Cell Communication and Multicellularity 10

Start Sperm entry point

Red color indicates calcium ions

Finish

7.14 Calcium Ions as Second Messengers (Page 135)

1 Acetylcholine binds to receptors on endothelial cells of blood vessels; activation of the receptor Outside of cell causes production of IP3.

Acetylcholine 2+ (ACh) 3 Ca stimulates NO synthase, the enzyme that makes nitric oxide gas (NO) from arginine. Blood vessel

Endothelial cell Smooth muscle

NO synthase Acetylcholine 4 NO diffuses to the smooth receptor (AChR) muscle cells, where it P stimulates cGMP synthesis. P IP3 Ca2+ NO LIFE The ScienceInside of of Biology cell 9E Sadava P Arginine Sinauer Associates Guanylyl Morales Studio P cyclase Figure 07.16 Smooth Date 04-20-09 ER P P NO 5 cGMP promotes cGMP muscle relaxation. + PP GTP i 2+ 2 IP3 opens Ca channels on the 2+ ER membrane, releasing Ca Smooth into the cytosol. muscle cell Ca2+ 7.15 Nitric Oxide in Signal Transduction (Page 136)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.15 Date 04-25-12 Chapter 7 | Cell Communication and Multicellularity 11

(A) ATP Protein kinase

P Inactive Active enzyme enzyme

Protein Pi phosphatase

(B) Receptor binding

Inactive Active G protein GDP GTP G protein

GTPase (C) Adenylyl cyclase Phosphodiesterase ATP cAMP AMP

7.16 Regulation of Signal Transduction (Page 136)

To brain

Brain

Nasal cavity Neuron Odorant molecules

LIFE The Science of Biology 10E Sadava Outside of cell 1 Binding of an odorant to Sinauer Associates its receptor activates a Morales Studio Odorant G protein. Figure 07.16 Date 04-25-12 2 The G protein activates cAMP causes ion molecule 3 the synthesis of cAMP. channels to open. Ca2+ Na+

GTP GTP Odorant G protein Adenylyl cAMP-gated 4 Changes in ion concentrations Na+ receptor cyclase channel ATP Ca2+ cAMP inside the cell initiate a signal Inside of cell to a specific area of the brain, which perceives the signal Signal to brain 7.17 A Signal Transduction Pathway Leads to the Opening of Ion Channels as a scent. (Page 137)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.17 Date 04-25-12 Chapter 7 | Cell Communication and Multicellularity 12

Outside of cell

1 Epinephrine Activated Epinephrine G protein Plasma receptor subunit membrane

Activated 1 Phosphorylation, induced by GTP adenylyl cyclase epinephrine binding, inactivates glycogen synthase, preventing ATP glucose from being stored as 20 cAMP glycogen.

Inactive protein kinase A Active glycogen synthase 20 Active protein kinase A Inactive glycogen Inactive phosphorylase kinase synthase

2 The protein kinase cascade amplifies the signal. Here, for every molecule of epinephrine 100 Active phosphorylase kinase bound, 20 molecules of cAMP are made, each of which activates a Inactive glycogen phosphorylase molecule of protein kinase A.

1,000 Active glycogen phosphorylase

Glycogen 3 Phosphorylation activates 10,000 Glucose 1-phosphate glycogen phosphorylase, releasing stored glucose molecules from glycogen. Glucose Inside of cell

4 Release of glucose fuels 10,000 “ﬁght-or-ﬂight” response. Blood glucose Outside of cell

7.18 A Cascade of Reactions Leads to Altered Enzyme Activity (Page 138)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.18 Date 04-25-12

(A) Plasma membranes

Cell 1 Cell 2

The connexons of two cells come together to form a narrow (~1.5 nm) channel through which ions and small signal molecules can pass.

Connexon

Space between cells (”gap”; ~2 nm) Connexins

(B)

Smooth Plasma endoplasmic reticulum Cell 1 membrane

Proteins Cell walls

Plasmodesma Desmotubule

Cell 2

7.19 Communicating Junctions (Page 139)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.19 Date 04-26-12

Chlamydomonas Gonium is a Pandorina is a larger is single-celled. cluster of cells. cluster of 16 cells.

Eudorina is a still larger Pleodorina has some cells Volvox is larger, with internal cluster of cells. specialized for reproduction. specialized reproductive cells.

7.20 Multicellularity (Page 140)

LIFE The Science of Biology 10E Sadava Sinauer Associates Morales Studio Figure 07.20 04-25-12