Essential Cell Biology 5th edition
Share Embed Flag
Download ePaper

Essential Cell Biology 5th edition

BioLogize
14.07.2022 Views

698 CHAPTER 20 Cell Communities: Tissues, Stem Cells, and CancerFigure 20–11 Incorrect collagen assembly can cause the skin tobe hyperextensible. James Morris, “the elastic skin man,” from aphotograph taken in about 1890. Abnormally stretchable skin is partof a genetic syndrome that results from a defect in collagen assembly.In some individuals, this condition arises from a lack of an enzyme thatconverts procollagen to collagen; in others, it is caused by a defect inprocollagen itself.intervening collagen becomes organized into a dense band of aligned fibersthat connect the two explants (Figure 20–13). The fibroblasts migrateout from the explants along the aligned collagen fibers. In this way, thefibroblasts influence the alignment of the collagen fibers, and the collagenfibers in turn affect the distribution of the fibroblasts. Fibroblasts presumablyplay a similar role in generating long-range order in the extracellularmatrix inside the developing body—in helping to create tendons, forexample, and the tough, dense layers of connective tissue that ensheatheand bind together most organs. Fibroblast migration is also important forhealing wounds (Movie 20.1).ECB5 e20.12/20.12Integrins Couple the Matrix Outside a Cell to theCytoskeleton Inside ItCells are able to interact with the collagen in the extracellular matrixthanks to a family of transmembrane receptor proteins called integrins.The extracellular domain of an integrin binds to components of thematrix, while its intracellular domain interacts with the cell cytoskeleton.This internal mooring provides a strong and stable point of attachment;without it, integrins would be easily torn from the flimsy lipid bilayer, andcells would be unable to anchor themselves to the matrix.Integrins do not, however, interact directly with collagen fibers in theextracellular matrix. Instead, another extracellular matrix protein,fibronectin, provides a linkage: part of the fibronectin molecule binds tocollagen, while another part forms an attachment site for integrins.When the extracellular domain of the integrin binds to fibronectin, theintracellular domain binds (through a set of adaptor molecules) to anactin filament inside the cell (Figure 20–14). For many cells, it is the formationand breakage of these attachments on either end of an integrinmolecule that allows the cell to crawl through a tissue, grabbing hold ofthe matrix at its front end and releasing its grip at the rear (see Figure17−33). Integrins coordinate these “catch-and-release” maneuvers byundergoing remarkable conformational changes. Binding to a moleculeon one side of the plasma membrane causes the integrin molecule tostretch out into an extended, activated state so that it can then latchonto a different molecule on the opposite side—an effect that operatesin either direction across the membrane (Figure 20–15). Thus, an intracellularsignaling molecule can activate the integrin from the cytosolicside, causing it to reach out and grab hold of an extracellular structure.Similarly, binding to an external structure can switch on a variety of intracellularsignaling pathways by activating protein kinases that associatewith the intracellular end of the integrin. In this way, a cell’s externalattachments can help regulate its behavior—and even its survival.5 µmFigure 20–12 Collagen fibrils in the skin of some animals arearranged in a plywoodlike pattern. The electron micrograph showsa cross section of tadpole skin. Successive layers of fibrils are laiddown nearly at right angles to each other (see also Figure 20–9). Thisarrangement is also found in mature bone and in the cornea, but not inmammalian skin. (Courtesy of Jerome Gross.)

Extracellular Matrix and Connective Tissues699heartexplantmigrating fibroblastsFigure 20–13 Fibroblasts influencethe alignment of collagen fibers. Thismicrograph shows a region between twopieces of embryonic chick heart (rich infibroblasts and heart muscle cells), whichhave grown in culture on a collagen gel forfour days. A dense tract of aligned collagenfibers has formed between the explants,presumably as a result of the fibroblasts,which have proliferated and migrated outfrom the explants, tugging on the collagen.Elsewhere in the culture dish, the collagenremains disorganized and unaligned, so thatit appears uniformly gray. (From D. Stopakand A.K. Harris, Dev. Biol. 90:383–398, 1982.With permission from Elsevier.)aligned collagen fibers1 mmHumans make at least 24 kinds of integrins, each of which recognizesdistinct extracellular molecules and has distinct functions, dependingon the cell type in which it resides. For example, the integrins on whiteECB5 e20.14/20.14blood cells (leukocytes) help the cells crawl out of blood vessels at sitesof infection so as to deal with marauding microbes. People who lack thistype of integrin develop a disease called leucocyte adhesion deficiency andsuffer from repeated bacterial infections. A different form of integrin isfound on blood platelets, and individuals who lack this integrin bleedexcessively because their platelets cannot bind to the necessary bloodclottingprotein in the extracellular matrix.Nextracellular matrixbinding site(e.g., via collagen)Ncollagen fibrilfibronectincell attachment site(e.g., via integrin)fibronectinintegrin dimer(A)S S C Cplasmamembraneadaptorproteins5 nmCYTOSOL(B)(C)actinfilament50 nmFigure 20–14 Fibronectin and transmembrane integrin proteins help attach a cell to the extracellular matrix. Fibronectinmolecules bind to collagen fibrils outside the cell. Integrins in the plasma membrane bind to the fibronectin and tether it to thecytoskeleton inside the cell. (A) Diagram and (B) electron micrograph of a molecule of fibronectin. (C) The transmembrane linkagemediated by an integrin protein (blue and green dimer). The integrin molecule transmits tension across the plasma membrane: itis anchored inside the cell via adaptor proteins to the actin cytoskeleton and externally via fibronectin to other extracellular matrixproteins, such as the collagen fibril shown. The integrin shown here links fibronectin to an actin filament inside the cell. Other integrinscan connect different extracellular proteins to the cytoskeleton (usually to actin filaments, but sometimes to intermediate filaments).(B, from J. Engel et al., J. Mol. Biol. 150:97–120, 1981. With permission from Elsevier.)

Extracellular Matrix and Connective Tissues

699

heart

explant

migrating fibroblasts

Figure 20–13 Fibroblasts influence

the alignment of collagen fibers. This

micrograph shows a region between two

pieces of embryonic chick heart (rich in

fibroblasts and heart muscle cells), which

have grown in culture on a collagen gel for

four days. A dense tract of aligned collagen

fibers has formed between the explants,

presumably as a result of the fibroblasts,

which have proliferated and migrated out

from the explants, tugging on the collagen.

Elsewhere in the culture dish, the collagen

remains disorganized and unaligned, so that

it appears uniformly gray. (From D. Stopak

and A.K. Harris, Dev. Biol. 90:383–398, 1982.

With permission from Elsevier.)

aligned collagen fibers

1 mm

Humans make at least 24 kinds of integrins, each of which recognizes

distinct extracellular molecules and has distinct functions, depending

on the cell type in which it resides. For example, the integrins on white

ECB5 e20.14/20.14

blood cells (leukocytes) help the cells crawl out of blood vessels at sites

of infection so as to deal with marauding microbes. People who lack this

type of integrin develop a disease called leucocyte adhesion deficiency and

suffer from repeated bacterial infections. A different form of integrin is

found on blood platelets, and individuals who lack this integrin bleed

excessively because their platelets cannot bind to the necessary bloodclotting

protein in the extracellular matrix.

N

extracellular matrix

binding site

(e.g., via collagen)

N

collagen fibril

fibronectin

cell attachment site

(e.g., via integrin)

fibronectin

integrin dimer

(A)

S S C C

plasma

membrane

adaptor

proteins

5 nm

CYTOSOL

(B)

(C)

actin

filament

50 nm

Figure 20–14 Fibronectin and transmembrane integrin proteins help attach a cell to the extracellular matrix. Fibronectin

molecules bind to collagen fibrils outside the cell. Integrins in the plasma membrane bind to the fibronectin and tether it to the

cytoskeleton inside the cell. (A) Diagram and (B) electron micrograph of a molecule of fibronectin. (C) The transmembrane linkage

mediated by an integrin protein (blue and green dimer). The integrin molecule transmits tension across the plasma membrane: it

is anchored inside the cell via adaptor proteins to the actin cytoskeleton and externally via fibronectin to other extracellular matrix

proteins, such as the collagen fibril shown. The integrin shown here links fibronectin to an actin filament inside the cell. Other integrins

can connect different extracellular proteins to the cytoskeleton (usually to actin filaments, but sometimes to intermediate filaments).

(B, from J. Engel et al., J. Mol. Biol. 150:97–120, 1981. With permission from Elsevier.)

logo

products

Resources

Company

Terms of service
Privacy policy
Cookie policy
Cookie settings
Imprint
Change language
Made with love in Switzerland
© 2024 Yumpu.com all rights reserved

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!