The Nucleus
The nucleus is a membrane-limited compartment that contains the
Genome (genetic information) in eukaryotic cells, so it is responsible
to direct all the metabolic activities of the cell.
It is a large membrane bound structure that present in all cells
except the red blood cells where they lose their nuclei when they
mature.
Most cells possess a single nucleus, but others may be binucleate
such as cardiac muscle cells , or multinucleate as skeletal muscle
cells .
The shape of the nuclei differ with cell shape ,it may be rounded or
elongated but it is usually spherical .
The location of it is usually in the center of the cell , they are differ in
diameter between (5-10 Mm) and in some cells it could reach more
than (25 Mm) in diameter such as ovum .
The nucleus stain blue when using basophilic dye as hematoxylin ,
and it is basophilic in nature ,due to its content of nucleic acid (DNA)
and basic protein (histone) .
The nucleus is surrounded by nuclear envelope , it is filled with
nuclear matrix (karyoplasm) and contain nuclear chromatin and a
nucleolus .
1) Nuclear envelope :
In the light microscope ,a nuclear membrane observed as a thin line
surrounding the nucleus .
Electron microscopy ,shows that the nucleus is surrounded by two
parallel unit membranes separated by a narrow space ( 30_50 nm)
called the perinuclear cisterna or perinuclear space , that serves as
a membranous boundary between the nucleoplasm and the
cytoplasm of the cell .
The outer membrane is frequently attached with ribosomes , and
this portion of it is sometimes continuous with the rough
endoplasmic reticulum RER where involve in protein synthesis .
The inner membrane of nuclear envelope is closely associated with
protein structure called Fibrous lamina or nuclear lamina with
thickness (80-300 nm) .
This lamina composed of polypeptides called lamins that are type of
an intermediate filament and form part of the nuclear matrix , this
form a structure to maintain the spherical shape .
Around the nuclear envelope , at sites where the inner and outer
membranes fuse , to produce circular gaps ,called nuclear pores (70
nm).
Each pore possesses eight protein subunits arranged in an octagonal
annulus or ring at the periphery of the pore with filaments
extending into both the cytoplasm and the nucleus , to form the
nuclear pore complex NPC .
Each complex contains about 30 different proteins which referred
to as nucleoporins .
This complex mediated Bidirectional Nucleocytoplasmic Transport,
and this transport occur through nuclear pores by passive diffusion
of ions and small molecules while large molecules and molecular
complexes are pass by the following process: (( proteins that
wanted to be imported are bound by soluble import receptor
proteins and the resulting complexes then attach to the filaments of
nucleoporins on the cytoplasmic face of the NPC. Translocation
occur by repeated interactions with a series of discrete binding sites
along these nucleoporin filaments, beginning on the cytoplasmic
face, then in the pore itself, and finally on the nucleoplasmic side of
the NPC.))
Export of RNA and ribosomal subunits from the nucleus depends on
a similar system of export signals and export receptor proteins
binding the nucleoporins.
It provide pathway between the nucleus and the cytoplasm through
which material can pass into or out of the nucleus , so it serves in
the transport of ribosomal proteins that are incorporated into
ribosomes in the nucleolus ,as well as the nuclear proteins such as
histone and lamins that are produced in the cytoplasm , into the
nucleus .
Similarly , mRNAs and ribosomes must exit the nucleus to reach the
cytoplasm by the same route.
The number of nuclear pore vary from cell to cell, increasing in
cells actively involved in protein synthesis .
The nucleus of a typical mammalian cell contains 3000—4000 such
pore complexes , each composed of subunits with 30 different NPC
proteins or nucleoporins .
2) The Nucleolus :
The nucleolus is a non-membranous , intranuclear structure formed
by filamentous and granular material .
It varies in size ( 1-3 Mm ) in diameter , being well develop in cells
active in protein synthesis , also in embryonic cells during
proliferation and rapidly growing malignant tumors , in some cells
there may be more than one nucleolus .
It consist largely of RNA and protein and it is the site of synthesis
the subunits of ribosomal RNA that associated with many ribosomal
proteins which are imported from the cytoplasm through the
nuclear pore complex then leave the nucleus by nuclear pores to be
assembled into functional ribosomes in the cytoplasm .
The nucleolus is basophilic when stained with Hematoxylin and
Eosin .
The nucleolus consist of three distinct components :
1) One to several pale staining regions which composed of
Nucleolar organizer DNA- sequences of bases that code for
rRNA (ribosomal ribonucleic acid ) .
2) Pars fibrosa which appear as pale region composed of ( 5 – 10
nm ) ribonucleoprotein fibers ,it is consist primary transcripts
of rRNA genes , it is the site of ribosomal subunits formation
which then mature in the granular region .
3) Pars granulosa that consist of dense granules ( 15 – 20 nm )
which are maturing ribosomes, it contain maturing ribosomal
subunit particles.
The network formed by pars granulosa and pars fibrosa is called the
nucleonema . The DNA that is responsible for the synthesis of the
ribosomal subunits is localized in the interstices of that network.
3) The nuclear matrix :
It is semi- fluid matrix that fill the space between the chromatin and
the nucleolus .
It is composed mainly of proteins (some have enzymatic activity )
,metabolites and ions .
It is also contain dispersed chromatin and fibrous lamina of the
nuclear envelope .
The function of the nuclear matrix is still being studied , in fact , it
1- binds to hormone receptors
2- serve as medium for diffusion of metabolites larger molecules .
When the nucleic acids and other soluble components of the
nuclear matrix are removed , a continuous fibrillar structure
remains , forming the nucleoskeleton .
The nucleoskeleton :
1- contributes to the formation of a protein base to which DNA
loops are bound
2- regulated the assemble and disassemble of the nuclear
membrane during cell division .
4) The Chromatin :
The chromatin is a loosely coiled fibers that dispersed through the
nucleus .
It consist of coiled strands of DNA ( deoxyribonucleic acid ) bound to
basic proteins histones which play a role in the regulation of DNA
functions .
The chromatin is usually arranged in repeating units of small
particles called nucleosome , which are found in both euchromatin
and heterochromatin and in chromosomes , it is a particle of about
(10 nm) diameter consis ng of a core of eight (four sets ) histone
molecules (H2A, H2B , H3 , H4 ) around this octamer wrapped two
loops of DNA with about 150 base pairs .
Each nucleosome also has a larger linker histone (H1 ) that binds
both wrapped DNA and the surface of the core .
The series of nucleosomes in chromatin is also associated with
many diverse non histone proteins with a wide variety of enzymatic
function
The DNA extends between each par cle as a (1.5 nm ) filament that
joins adjacent nucleosomes .
There are two types of chromatin can be distinguished under the
electron microscope :
1-Euchromatin : ( dispersed less – coiled chromatin )
It is visible under the EM only , it is an electron – lucent area , light
staining appear as loose network of fine fibrils .
It is metabolically active , which play an important role in
transmission of genetic informations and in protein synthesis .
2- Heterochromatin : ( condensed or coiled chromatin )
It is visible under light microscope LM as a basophilic clumps of
nucleoprotein .
Under EM , it is appear as an electron – dense area composed of
coarse granules .
It is metabolically inert , it could be involve in cytoskeleton
function .
The distribution of this chromatin include three locations :
1. Marginal chromatin : It is found as a thin peripheral layer
which lines the inner nuclear envelope .
2. Karyosome : As patches scatter in the nucleoplasm .
3. Nucleolar associated chromatin : Found as a rim condensed
chromatin in association with the nucleolus .
In dividing somatic (mitotic) cells ,chromatin is condensed and
organized into discrete bodies called chromosomes .
The proportion or amount of euchromatin & heterochromatin
usually indicate the metabolic activity .
The nucleoprotein of the chromatin is coiled and the degree of
coiling varies during the cell activity .
The chromatin pattern of a nucleus indicate the cell activity . The
cells with light nuclei ( with few heterochromatin clumps ) are more
active where more DNA surface available for the transcription of
genetic information . While the cells with darkly nucleus ( the coiling
of DNA makes less surface available for the transcription of genetic
information) therefore less active .
Sex chromatin ( Barr body )
Human male soma c cells have ( 46 ) chromosomes arranged in 23
pairs . 22 pairs are called autosomes and 1 pair is formed by X & Y or
sex chromosomes .
Each of these 23 pairs of chromosomes contains one chromosome
originally derived from the mother and one derived from the father
Soma c cells are considered diploid (2n) because they contain
paired chromosomes . Sperm cells and mature oocytes are haploid ,
with half the diploid number of chromosomes (n) , each pair of
chromosomes having been separated during meiosis .
In female , there are 22 pairs of autosomes and two X chromosomes
, one of these X chromosomes is extremely heterochromatic and
forms a visible tightly coiled mass in the interphase nucleus .
This small visible mass is called Barr body or Sex chromatin . It is
about ( 1 Mm ) in diameter , whereas the other X chromosome is
uncoiled and not visible .
The coiling of this chromosome explain why it is easily stained and
can be observed with light microscope .
Evidence suggests that the coiled X chromosome including the sex
chromatin is genetically inactive , the X chromosome inactivation
involves a number of specific chemical modifications of its histones .
In male , there are 22 pairs of autosomes and one pair of sex
chromosome include X & Y chromosome as sex determinants . The
X chromosome is uncoiled , therefore no sex chromatin is visible , so
Barr body is not seen in a normal male somatic cells .
The Barr body appear clearly in epithelial cells as a small granule
attached to the nuclear envelope . It is seen well in nuclei of
squamous epithelial cells that lining the internal surface of the
cheek or buccal cavity .
Blood smears are also used , in which case the sex chromatin
appears as drumstick – like appendage attached to the nuclei of the
neutrophilic leukocytes .
The study of sex chromatin has wide application in medicine ,
because it :
1- permits determination of genetic sex in doubtful cases
2- in patients whose external sex organs do not give assignment of
gender as in hermaphroditism and pseudohermaphroditism .
Sex chromatin is essential for the study of other anomalies involving
the sex chromosomes that include :
1-Kline Felter syndrome : XXY chromosomes ( male represent
female properties ) , in which testicular abnormalities ,
azoospermia ( absence of spermatozoa ) , and other symptoms
are associated .
2-Turnurs syndrome : XO (female represent male properties ) .
Karyotype : Is the number and characteristics of chromosomes
encountered in an individual.
