Fig. 1.8 Movementofsmallmoleculesandlargerstructuresacrossmembranes.Thelipidbilayerisrelativelyimpermeabletoallbutthesmallestand/ormosthydrophobicmolecules.Thus,theimportorexportofchargedspeciesrequiresspecifictransmembranetransporterproteins;theinternalizationorexternalizationoflargeproteins,complexparticles,orevencellsrequiresencirclingthemwithsegmentsofthemembrane.Smallchargedsolutescanmoveacrossthemembraneusingeitherchannelsorcarriers;ingeneral,eachmoleculerequiresauniquetransporter.Channels areusedwhenconcentrationgradientscandrivethesolutemovement.Carriers arerequiredwhensoluteismovedagainst aconcentrationgradient.Receptor-mediatedandfluid-phaseuptakeofmaterialinvolvesmembrane-boundvacuoles.Caveolae endocytoseextracellularfluid,membraneproteins,andsomereceptor-boundmolecules(e.g.,folate)inaprocessdrivenbycaveolinproteinsconcentratedwithinlipidrafts.Pinocytosis ofextracellularfluidandmostsurfacereceptor–ligandpairsinvolvesclathrincoated pits and vesicles.Afterinternalization,theclathrindissociatesandcanbereused,whereastheresultingvesicleprogressivelymaturesandacidifies.Intheearlyand/orlateendosome,ligandcanbereleasedfromitsreceptor(e.g.,ironreleasedfromtransferrinboundtothetransferrinreceptor)withreceptorrecyclingtothecellsurfaceforanotherround.Alternatively,receptorandligandwithinendosomescanbetargetedtofusewithlysosomes(e.g.,epidermalgrowthfactorboundtoitsreceptor);aftercompletedegradation,thelateendosome–lysosomefusionvesiclecanreconstitutelysosomes.Phagocytosis involvesthenon–clathrin-mediatedmembraneinvaginationoflargeparticles—typicallybyspecializedphagocytes(e.g.,macrophagesorneutrophils).Theresultingphagosomeseventuallyfusewithlysosomestofacilitatethedegradationoftheinternalizedmaterial.Transcytosis involvesthetranscellularendocytotictransportofsoluteand/orboundligandfromonefaceofacelltoanother.Exocytosis istheprocessbywhichmembrane-boundvesiclesfusewiththeplasmamembraneanddischargetheircontentstotheextracellularspace.
are concentrated in secretory vesicles, which then fuse with the plasma membrane and expel their contents.
Transcytosis is the movement of endocytosed vesicles between the apical and basolateral compartments of cells; this is a mechanism for transferring large amounts of intact proteins across epithelial barriers (e.g., ingested antibodies in maternal milk across intestinal epithelia) or for the rapid movement of large volumes of solute. In fact, increased transcytosis probably plays a role in the increased vascular permeability seen in tumors.
We now return to the two forms of endocytosis mentioned earlier.
• Caveolae-mediated endocytosis. Caveolae (“little caves”) are noncoated plasma membrane invaginations associated with GPI-linked molecules, cyclic adenosine monophosphate (cAMP)-binding proteins, SRC-family kinases, and the folate receptor. Caveolin is the major structural protein of caveolae. Internalization of caveolae with any bound molecules and associated extracellular fluid is denoted potocytosis—literally “cellular sipping.” Although caveolae likely participate in the transmembrane delivery of some molecules (e.g., folate), they also appear to contribute to the regulation of trans-membrane signaling and/or cellular adhesion via the internalization of receptors and integrins. Mutations in caveolin are associated with muscular dystrophy and electrical abnormalities in the heart.