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Cell Biology 1:Membranes, Cytoplasm and Nucleus
Medical Microanatomy 602Edie C. Goldsmith, Ph.D.
M=mitochondriaER=rER N=nucleusNE=nuclear membraneG=golgi apparatusV=vesicles PM=plasma membraneC=neighboring cell IS=intercellular spaceL=lysosome See Table 2.1 pg 24-25 in your textbook
Plasma Membrane8-10 nm thickFunctionSelective barrierCell adhesionCommunicationThree main componentsPhospholipidsProteins (integral or peripheral)Cholesterol
Modified Fluid Mosaic Model
LipidsMembranes usually have 40-60% lipidType variesPhosphatidylcholine, phosphatidylserine, phosphatidylethanolamineglycolipidsPolar and non-polar groupsSaturated vs unsaturatedNot uniform distributionrafts
Lipid RaftsEnriched in Cholesterol and Sphingolipids
Less fluid than typical membrane
Due to the amphipathic nature of lipids - self associateMicellesBilayersLipids can move within a bilayer
CholesterolIntegrates into bilayerAmount in PM can vary by cell type
Modulates membrane fluidity
Membrane Proteins~50% of membrane (w/w)Two general typesIntegralPeripheralProteins are also asymmetrically distributed with respect to the lipid bilayer
Multiple categories of integral membrane proteinsPumps and enzymes (ion pumps)Channels (gap junctions)ReceptorsLinker (integrins)Carrier proteinsStructural ProteinsGlycoproteins and glycolipidsglycocalyx
Freeze-fractureThe interior of the lipid bilayer is weak and readily split by simple cleavage.Membrane proteins will stay with one or the other bilayer forming bumps and leaving pits.
Freeze FractureThe two faces of the cleaved lipid bilayer may be examined using freeze fracture to help determine membrane protein distribution.Imaged by TEM
TEM vs. Freeze FractureTop: Gap junction between plasma membranes of two cells
Middle/bottom: same structure viewed en face using freeze fracture
Transport MechanismsDiffusion - Passive and FacilitatedPassive concentration gradientGases, lipids, lipid soluble molecules (i.e. EtOH) Facilitated concentration dependentRequire protein carrier molecule; does not require energyGlucose and amino acids (hydrophilic)Active transportRequires energy (ATP)Movement against gradientNa+-K+ATPaseChannel ProteinsSmall, water soluble moleculesProteins create pore in membrane; ion selectiveRegulated by membrane potential (voltage-gated), neurotransmitters (ligand-gated), mechanical stress
Transport MechanismsVesicular transportEndocytosisPinocytosisReceptor mediated endocytosisPhagocytosisExocytosis
Receptor-mediated EndocytosisReceptor mediatedLDL, transferrin/Fe, EGFClathrin dependentAssemble on cytoplasmic side of membraneWeave-like networkCoated pitsFuse with endosomesdynamin
PhagocytosisMacrophages and polymorphonuclear leukocytesEngulfment of large particles~ 250 nmBacteria, protozoa, fungi, damaged cellsNon-biological debrisClathrin independent actin dependentReceptor mediatedFc receptors
Pinocytosiscell drinkingClathrin independentSmooth vesicles80-150 nmIntake of fluid and small moleculesUsually fuse with lysosomesBulk transfer (endothelial cells)
ExocytosisMechanism for releasing molecules into extracellular spaceTwo pathwaysConstitutiveAll cellsSecreted immediately; No granulesSecretorySpecialized cellsProteins to be secreted stored in vesicles
CytoplasmAqueous matrix containing organellesAbout total volume of cell
Cytoskeleton
Site of many metabolic pathwaysGlycolysis, protein synthesis
Nucleus3-10 mmUsually largest organelleFunctionGenome, production of ribosomes and mRNAMultiple nucleiNot always in center of cellNot always roundMultiple componentsChromatinNucleolusNuclear envelopNucleoplasm
Reticulocytes lose the nucleus entirely to become mature RBCsMuscle cells have multiple nuclei
ChromatinDNA-protein complexhistonesBasophilic staining of nucleiHeterogenousHeterochromatin - highly condensed (dense appearance)Cell inactiveEuchromatin - dispersed (light appearance)Active cell
Some cells are very inactive, and their nuclei contain mostly heterochromatin.This is a late red blood cell precursor
NucleusThe nucleus shown in this image appears in four parts.
Can cells have multiple nuclei? Does this cell have multiple nuclei?
ChromosomesSee Folder 3.1 pg 80-81
NucleolusNo membraneBasophilicThree components Fibrillar material/region (Pars fibrosa) active transcription of rRNA genes; lots of rRNAGranular material/region (Pars granulosa) ribosomal assemblyFibrillar centers regions of DNA that code for rRNA, RNA Pol I, transcription factorsNucleolar organizer regionNOR
Nucleoli are the site of rRNA synthesisMay vary greatly in size and appearanceActive cells may contain multiple nucleoli
Light microscopy of Primary Oocytes
Nuclear EnvelopeTwo membranes separated by narrow space (perinuclear cisterna)Outer membrane contiguous with rERInner membrane associated with nuclear laminaLamins (A and C) provide stability and association points for chromosomesLamin mutations can affect striated muscle, adipose tissue, nerve/skeletal development
Nuclear Pores70 - 80 nm openingsNumber and distribution varyOnly site of direct molecular exchange with cytoplasm
Freeze fracture demonstrating distribution of nuclear pores
> than 50 subunitsRegulates bidirectional protein translocationIons & < 9 daltons freelyLarge proteins/complexes, RNA, ribosomal subunits require GTPRequire nuclear localization signal (NLS) to get inNuclear export sequence (NES) to get out
Cell CycleCell populationStatic - no divisionStable - sporadicRenewing - regular divisionSlow (smooth muscle) or rapid (dermal fibroblasts)Cell CycleMitosisInterphase
InterphaseThree phasesG1Longest phase (9-12 hours)Two checkpoints restriction point and DNA damage checkpointS7.5-10 hoursDNA damage checkpoint fidelity of replicationG23.5-4.5 hoursCell growth and organelle organizationTwo checkpoints Unreplicated DNA and DNA damage G0/Terminal Differentiation
MitosisFour stages (~ 1hr)Two checkpoints spindle assembly (anaphase) & chromosome segregation (prior to cytokinesis)ProphaseChromosomes condenseLoss of nucleolus and nuclear membraneMetaphaseAssembly of mitotic spindleChromosomes migrate to equatorial planeAnaphaseChromatids separate and migrate toward polesTelophaseNuclear membrane and nucleoli reappear; cytokinesisIPMA
Cell Cycle RegulationEntry into different phases is controlled by cyclins and cyclin-dependent kinases (Cdks)2-protein complexSynthesis oscillates up and down during cell cycle
ApoptosisNormal part of developmentCharacteristicsDNA fragmentationDecrease in cell & nucleus sizeLoss of mitochondrial functionMembrane blebbingApoptotic bodiesNecrosisPathologic processCharacteristicsDamage to plasma membraneSwellingCell lysisInflammatory response
Apoptosis vs Necorsis
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