MODULE 1: CELL, CELLULAR ACTIVITIES, CELL MEMBRANE

I. CELL - basic structural and functional units of all multicellular organisms

A. Structure
i. Nucleus
ii. Cytoplasm
1. Formed Elements
a) rganelles
b) Inclusions
i. Crystals - found in sertoli and leydig
ii. !igment granules
1. Lipofuscin - bro"nis# gold seen in nondi$iding cells% result of aging
&. 'emosiderin - indigestible residues of 'b% p#agocytosis of ()Cs
iii. Stored products *glycogen+ lipids)
&. Cytosol
a) ions *Na+ ,+
Ca) - pro$ide inorg c#emicals for cell r-n% cell control mec#anism
b) org mols
i. Carbs *glucose+ glycogen) - part of glycoproteins% more on nutrition
ii. Lipids *&.) - form membrane and intracellular barriers
1. !#osp#olipids
&. C#olesterol
/. 0riglycerides *neutral fat) - store#ouse of energy
iii. !roteins *11-&1.)
1. Structural - long filaments% form microtubules 2 cytos3eleton
&. Functional - tubular-globular% en4ymes% mobile
c) "ater *51-67.)
). rganelles
iii. 8embranous - "it# plasma membrane


i$. Nonmembranous - proteins self-assemble into polymers 2 cytos3eleton
9fibrillar proteins - synt#esi4ed in t#e ribosome% form filament or tubule
9ectoplasm - outer 4one of t#e cytoplasm% actin filament
- form elastic support for t#e cell membrane
C. Nucleus
i. C#romatin - contains :NA *1.6m) and fi$e proteins *#istone and non-#istone)% basop#ilic *p#osp#ate grps)
1. Euc#romatin - dispersed% lig#tly staining *not $isible in L8 or ;clear areas<)
- acti$e c#romatin *stretc#ed out)
- neurons+ li$er cells
&. 'eteroc#romatin - condensed% densely staining
- stains "it# basic dyes *#emato-ylin)+ Feulgen *for deo-yribose)+
fluorescent *'oesc#t% propidium iodide)
- sperm+ lymp#ocytes+ plasma cells
a) 8arginal - perip#eryof t#e nucleus
b) ,aryosomes - t#roug#out t#e nucleus *irreg in si4e = s#ape)
c) Nucleolar-associated
9:NA 2 c#romatin 2 c#romosome *>?) - && pairs autosome+ 1 pair se- c#romosome
9pac3aging - to permit transcription to access regions of c#romosome re@ for gene e-pression
9'uman genome - entire lengt# of :NA containing info pac3aged in all >? c#romosomes
9gene - union of genomic se@uences encoding a co#erent set of potentially functional products
9:NAA#istone 2 nucleosome - 11-nm+ 1
st
le$el% :NAcoiling around a protein core% s#ortens 5fold
- core consists of 6 #istones *octamer) 2 /1-nm fibril 2 loop domainsBscaffold
9se- c#romosomes - C and D 22 CC *females) and CD *males)
9c#romosomes are stained "it# Eiemsa or FIS'
ii. Nucleolus - contains :NA in t#e form of r(NA genes+ (NA+ and proteins% site of r(NA synt#esis%
- contains regulatory cell-cycle proteins
iii. Nuclear en$elope - innerBouter membrane+ perinuclear cisternal space+ pores
9outer membrane connects "it# rE(
i$. Nucleoplasm
SignificanceF tumor diagnosis+ cell deat#
9 3aryolysis - disappearance of nuclei *:NAse)
9 py3nosis - c#romatin condensation 2 nuclear s#rin3age
9 3aryorr#e-is - fragmentation of nuclei
:. Cytos3eleton
a) 8icrotubules - rigid #ollo" tubes t#at can disassemble t#en reassemble
- gro" from y-tubulin rings "it#in 80C near t#e nucleus e-tending to t#e perip#ery
- Gparts of a-tubulin *non-gro"ing+ embedded in 80C) and b-tubulin *gro"ing+ e-t perip#ery)
-circularly arrayed globular dimeric tubulin molecules *protofilament2s#eet2cylinder)
-polymeri4ation needs E0! and 8g
-dynamic instability - adding and remo$ing of tubulin dimers 2 c#ange in lengt#
-f-nF lin3 perip#eral structures and organelles "it# 80C+ transport+ mo$ement+ cell asymmetry
9motor proteins - attac# to organelles *guide to destination)
:yneins - mo$e to"ard t#e minus end *from perip#ery to 80C)
,inesins - to"ard t#e plus end *from center to perip#ery)
Astral microtubule - nucleated from y-tubulin in a starli3e fas#ion
!olar microtubule - gro" a"ay from 80C
,inetoc#ore microtubule - probes cytoplasm in searc# for 3inetoc#ores

b) Intermediate filaments *6-11nm diameter) - s#o" di$ersity and tse specificity

-assembled from 1 pair of #elical monomers 2 t"ist around *coiled-coil dimer) 2 t"ist in
antiparallel fas#ion *staggered tetramer)
-f-nF compose cytoplasmic lin3 of tissue"ide continuum of cytoplasmic+ nuclear+ and
e-tracellular filaments% cell-to-cell = cell-to-e-tracellular matri-
-classesF
1 *acid) = & *basic) G 3eratins *of simple epit#+ of strat epit#+ structural)
- #eteropolymers
- keratoderma disorders
/ - #omopolymers
- Alexander disease, desmin-rel myopat#y
- contains four proteinsF
Himentin - most "idely distributed *mesoderm-deri$ed cells - fibroblast)
:esmin - muscle cells
Elial fibrillary acidic protein *EFA!) - astrocytes
!erip#erin - perip#eral ner$e cells
> - ;neurofilaments< - #eteropolymers - a-ons of ner$e cells - Parkinson dse
7 - nuclear lamins - nucleoplasm of almost all differentiatied cells
- Limb gurdle muscular dystrophy
? - lens-specific B beaded filaments - Congenital cataracts
!#a3inin
Filensin
c) 8icrofilaments *or Actin) - ?-6nm
- fast-gro"ing end G barbedBplus end
- slo"-gro"ing G pointedBminus end
- polymeri4ation re@F ,+ 8g+ A0! *#ydrolysis after E-actin incorporates to t#e fil)
- proteinsF
E-actin *globular) - free actin mols in t#e cytoplasm
F-actin *filamentous) - polymeri4ed
Actin-binding proteins - en#ance or pre$ent polymeri4ation
Actin-bundling proteins *fascin = fimbrin) - cross-lin3 creating filament
bundles+ imparts rigidity to t#e micro$illi
E. Intercellular communication
1. C#emical composition of ad#esion molecules
&. Structural connections *epit#elium)
/. !#ysical connections
a) Neural - neurotransmitters released by a-on terminals into synaptic Iunctions 22 ner$e cell f-n
b) Endocrine - influence f-n of a target cellat anot#er location in t#e body
c) !aracrine - adIacent communication *neig#boring cells)
II. CELL :IHISIN = 0'E( AC0IHI0IES
A. Cell :i$ision
a) Amitosis
b) 8itosis - c#romosome segration and nuclear di$ision 2 cell di$ision 2 & daug#ter cells "B t#e same n and d
- gat#ers proteins and (NA for :NA synt#esis 2 restriction point = :NA damage c#ec3 point
i. S p#ase - before mitosis+ cells duplicate :NA
ii. !rop#ase - c#romosomes condense and become $isible
- nuclear en$ disintegrates + nucleolus disappears *late prop#ase)
- c#romatids #eld by co#esins and centromeres
iii. 8etap#ase - mitotic spindle at opposite poles
- formation of e@uatorial or metap#ase plate
i$. Anap#ase - initial separation of sister c#romatids *pulled by dyneins+ co#esins brea3 do"n)
$. 0elop#ase - reconstitution of nuclear en$ around c#romosomes at eac# pole
- c#romosomes uncoil
- nucleoli reappear and cytoplasm di$ides 2 clea$age furro" *by contractile ring)
c) 8eiosis - & se@ nuclear di$isions 2 gametes containing 1n and 1d found in somatic cells
- significanceF reduction is necessary to maintain a constant J of c#romosomes
e-c#ange of c#romosome segments *crossing-o$er) 2 infinite genetic di$ersity
-p#ases in prop#ase in meiosis I
Leptotene - condensation of c#romatin *c#romosomes)
- sister c#romatids connect $ia meiosis-specific co#esion comple-es
- #omologous pairing is initiated
Kygotene - synapsis or close association of #omologous c#romosomes
- formation of synaptonemal comple- - binds c#romosomes toget#er
!ac#ytene - synapsis is complete 2 crossing-o$er
:iplotene - comple- dissol$es
- c#romosomes condense furt#er = separate but connected $ia c#iasmata
- c#iasmata indicates t#at crossing-o$er #as occurred
:ia3inesis - c#romosomes condense until ma-imum t#ic3ness
- nucleolus disappears
- nuclear en$elope disintegrates
). Cell 8o$ement - 8uscle cells *s3eletal+ cardiac+ smoot#)
a) Ameboid
i. 8ec#anism - continual formation of ne" cell membrane at t#e leading edge of t#e pseudopodium
- continual absorption of t#e membrane in mid and rear portions
- for"ard mo$ement 22 attac#ment of t#e pseudopodium to tissues *receptor proteins)
22 pro$ide t#e energy needed to pull cell body
ii. Control - c#emota-is as initiator *positi$e = negati$e)
9 t#e side of t#e cell t#at is most e-posed de$elops c#ange causing pseudopodial form-n
iii. Cells e-#ibit - L)Cs+ macrop#ages+ fibroblasts+ germinal cells of t#e s3in+ embryonic cells
b) Ciliary
i. 8ec#anism - "#ip-li3e mo$ement of cilia *layer of mucus mo$e 1cmBmin to"ard p#aryn-)
- a-oneme *comple- of tubules and lin3ages) re@uiresF
2 A0!
2 appropriate ionic conditions *8g and Ca)
2 dynein "it# A0!ase
ii. E-#ibit - respiratory air"ays = inside surfaces of uterine tubes
98o$ement "it#in cells
9Cytomorp#osis
C. Cell :eat#
a) Apoptosis - programmed cell deat#
- in$ proteolytic cascade *caspases) 22 cell s#rin3age and condensation 22 disassembled cytos3el
- controlled autodigestion or of neig#boring p#agocyte 22 no inIury to neig#boring cells
b) Necrosis - deat# due to acute inIury and damage to t#e plasma membrane 22 s"elling and lysis
- cause inflammation and inIury to neig#boring cells
:. C#emota-is - migration of cells to mo$e to"ard t#e source
- effecti$e up to 111 um a"ay from an inflamed tse
a) )acterialB$iral to-ins
b) :egenerati$e products of inflamed tissues
c) C7a
d) !lasma clotting reaction products
E. In = ut of t#e Cell
a) Endocytosis
i. !inocytosis - $ia small $esicles *171nm)
- consituti$e *continuous dynamic formation of small $esicles at t#e cell surface)
- 0E8F smoot# surface
- clat#rin-independent
ii. !#agocytosis - $esicles of 2&71um *p#agosome)
- membrane sends out pseudopodia to engulf particles
- receptor-mediated *Fc fragment)
- clat#rin-independent but actin-dependent
- clat#rin-dependent receptor-mediated endocytosis
b) E-ocytosis
i. Constituti$e secretory - subs are continuously deli$ered in transport $esicles to t#e C8
- proteins are secreted immediately after synt#esis *eg Ig from plasma cells)
- 0E8F cells lac3 secretory granules
ii. (egulated secretory - cells concentrate secretory proteins
- transiently store t#emin secretory $esicles
- stimulus 22 influ- of Ca 22 fusion of $esicles "it# C8
- cellsF endocrine+ e-ocrine+ neurons
9 cytologic anomaliesF
!olyploidy - more t#an & sets of c#romosomes
Aneuploidy - c#romosome number is not an e-act multiple of t#e J c#aracteristic of t#at species
:eletion -
NondisIunction -
0ranslocation-
III. CELL 8E8)(ANE
A. Lipids
a) !#osp#olipids *&7.)
i. !#osp#oglyceride - glycerol bac3bone attac#ed "it# & FA *ester) and "B p#osp#orylated alco#ol
ii. Sp#ingomyelin - sp#ingosine bac3bone attac#ed "it# FA *amide) 22 ceramide
- #ydro-yl grp of sp#ingosine is esterified to p#osp#orylc#oline 22 sp#ingomyelin
b) Elycosp#ingolipids
i. Cerebroside
ii. Eanglioside
c) C#olesterol *1/.) - fluidity of t#e membrane
9ot#er lipids *>.)
9carbs */.)
9FA - polar #ead% #ydrocarbon - #ydrop#obic
). !roteins *77.)
a) Integral - embedded "it#in bilayer% pass t#roug# bilayer
- re@uire detergents for solubili4ation
- lateral diffusion *lipid rafts) - pre$ents nonspecific interactions
9lipid rafts *ric# in c#olesterol+ sp#ingolipids+ and certain proteins) - in$ in signal transduction
- cell metabolism+ regulation+ and integration
2 pumps - transport ion acti$ely
2 c#annels - passi$e diffusion
2 receptors - recognition and locali4ed binding of ligands
2 lin3ers - anc#or intracellular cytos3eleton to e-tracellular matri-
2 en4ymes - A0!ase in ion pumping
2 structural - form Iunctions "it# neig#boring cells
b) !erip#eral - not embedded
- can be released by 0- "it# salt solns of #ig# ionic strengt#
- e-. An3yrin bound to integral band /
9glycoproteins - carbo#ydrate A protein
C. Asymmetry - location of carbs attac#ed to membrane proteins
- regional #eterogeneities - some macroscopically $isible *$illous borders of mucosal cells)
- asymmetry of p#osp#olipidsF p#osp#atidylc#olineBsp#ingomyelin M0SI:E
F aminop#osp#olipids INSI:E
- significanceF limited trans$erse mobility *flip-flop)
:. Fluid 8osaic 8odel - p#osp#olipids undergo rapid redistribution in t#e membrane *lateral diffusion)
22 p#ase c#anges 22 fluidity of t#e membrane *dependent upon lipid composition)
9transition temperature - temp at "#ic# structure undergoes transition from ordered to disordered
9c#olesterol modifies fluidityF t#e longer = more saturated $ia longer #ydrocarbons+ t#e #ig#er t#e 0m
- belo" 0m+ interferes "it# t#e interaction of t#e #ydrocarbon tails of FA 2 inc fluidity
- #ig#er 0m+ limits disorder becuase it is more rigid t#an t#e #ydrocarbon tails 22 cannot mo$e
9fluidity G permeability to "ater and small #ydrop#ilic mols
E. !roperties
Selecti$e permeability
1. Lipid bilayer
&. !rotein c#annels
Antigenicity
F. 0ransport System
i. :iffusion
a) Simple - mo$ement of molecules t#roug# interstices of bilayer or t#roug# "atery c#annels
Factors for rate of diffusionF
1. Amount of substance
&. Helocityof 3inetic motion
/. J and si4es of opening
b) Facilitated - re@uires a carrier protein
9Factors affecting net rate of diffusionF
1. Concentration difference
&. Electrical potential
/. !ressure difference
ii. Acti$e transport
-eg. Na-,-A0!ase pump
-/ Na receptors
-& , receptors
-A0!ase near Na receptors
-Secondary 0ransport
Co-transport - eg. Na-glucose
- primary acti$e transport of Na 2 #ig# conc gradient 2 store#ouse of energy
- diffusion energy of Na pulls glucose 2 conformational c#ange of protein
Counter transport - eg. Na-' in pro-imal tubules
- transport in a direction opposite to t#e primary ion
- Na to t#e inside+ ' to t#e outside
iii. Endo = e-ocytosis
0ransport according to J of molecules and direction of mo$ement
Mniport - mo$es 1 type of mol bidirectionally
Symport - & sol in t#e same direction *Na-glucose)
Anti-port - & sol in opposite directions *Na-Ca)
C#annel protein transport- contain a pore domain *ion-selecti$ity filter)
Holtage-gated - regulated by membrane potential *eg Na+ ,)
Ligand-gated - regulated by a specific moleculeBc#emical li3e neurotransmitters *eg acteylc#oline c#annel)