FUNCTIONAL MORPHOLOGY

OF THE CELL
Dr. dr. H. Busjra M. Nur MSc
Dept. Fisiologi FKUI / FKKUMJ

Main Cell Functions

Movement
Conductivity
Metabolic absorption
Secretion
Excretion
Respiration
Reproduction

Part of the Cell

Cell Membrane
Cytosol
Organelles
Nucleus

Cell Membrane
= plasma membrane
Separates the extracellular and
intracellular environments
Regulates molecular traffic into and out of
the cell channels and carriers
Sensitivity Receptor

Membrane Protein

Anchoring proteins
Recognition proteins
Enzymes
Receptors
Carrier proteins
Channels

Cytosol
Lots of potassium
Lots of protein (ec: enzyme)

Mitochondria
Oxidative phosphenylation ATP
Regulation of apoptosis
Hundreds to thousands in each eukaryotic
cells
Sausage shape in mammals
Have their own genom

Lysosomes
Is more acidic than the rest of cytoplasm
External material (endocytosed bacteria,
worn-out cell components) ingested in
them
When a lysosomal enzyme is congenitally
absent lysosomal storage diseases

Peroxisomes
Found in the microsomal fraction of cells
Surrounded by a membrane
The membrane contains a number of
peroxisome-specific proteins transport
of substances into / out of matrix of the
peroxisome
The matrix contains > 40 enzymes
catalyze a variety of anabolic / catabolic
reactions

Cytoskeleton

A system of fibers
Maintains the structure of the cell
Permits it to change shape and move
Made up of microtubules, intermediate
filaments and microfilaments and proteins
that anchor them and tie them together

Microtubules

Long, hollow structures

5 nm walls
A cavity 15 nm in diameter
Made up of two globular protein ( and
tubulin)
The assembly is facilitated by warmth and
disassembly by cold and other factors

Microtubules

Constant assembly and disassembly

dynamic portion of cell skeleton
The tracks for transport vesicles,
organelles (such as secretory granules)
and mitochondria from one part of the
cells to another
Form the spindle which moves the
chromosomes in mitosis

Microtubules

Microtubules assembly is prevented by

colchicine and vinblastine
Paclitaxel (Taxol), anticancer drug
binds to microtubules and makes them so
stable that organelles cannot move
mitotic spindles cannot form the cells
die

Intermediate filaments

8-14 nm in diameter
Connect the nuclear membrane to the cell
membrane
Form a flexible scaffolding for the cells
Help it resist external pressure
Absent: cells rupture more easily
Abnormal in humans: blistering of the skin

Microfilaments

Long, solid fiber, 4-6 nm in diameter

Made up of actin
Most abundant protein in mammalian cells
Attach to various parts of cytoskeletons
Reach to tips of the microvilli on the epithelial
cells of intestinal mucosa
Also in lamellopodia that cells put out when they
crawl along surfaces
Actin filaments interact with integrin receptors
and form focal adhesion complexes points of
traction with the surface cells pulls itself

Molecular Motors
Move protein, organelles, and other cell
parts (their cargo) to all parts of the cell
They attach to their cargo and their heads
bind to microtubules or actin polymers
Hydrolysis of ATP in their heads
molecules move
2 types: - producing motion along
microtubules
- producing motion along actin

Centrosomes
Microtubule-organizing centers (MTOGs)
contain -tubulin
When a cell divides centrosomes
duplicate themselves move apart to the
poles

Cilia
Unicellular: to propel themselves through
the water
Multicellular: To propel mucus and other
substances over the surface of various
epithelia

Cell adhesion molecules

- Attached cells to the basal lamina and other
cells cell adhesion molecules (CAMs)
- Important :
in embryonic development and formation of
the nervous system and other tissues
In holding tissues together in adult
In inflammation and wound healing
In the metastasis of tumors

Cell adhesion molecules

Many pass through the cell membrane

and are anchored to the cytoskeleton
inside the cell
Some bind like molecules on other cells
(homophilic binding)
Others bind to other molecules
(heterophilic binding)
Many bind to laminins (multiple receptors
domains in the extracellular matrix)

Cell adhesion molecules

Divided into
- integrins : heterodimers that binds to
various receptors
- IgG superfamily of immunoglobulins
- cadherins : Ca++ dependent molecule
cell to cell adhesion
- selectins : have lectin-like domains that bind
carbohydrates

Cell adhesion molecules

Fastens cells to their neighbors

Transmit signals into and out of the cells
Cells that lose their contact via integrins
apoptosis

Intercellular connections
Fasten the cells to one another and to
surrounding tissues
Permit transfer of ions and other
molecules from one cell to another

Nucleus
Made up of in large part of the chromosomes
The side where DNA and RNA are made
Cellular functions ultimately are controlled

The Chromosomes
Carry a complete blueprint for all the
heritable species and individual
characteristics
Occur in pairs, except in germ cells
Made up of a giant molecule of DNA
(deoxyribonucleic acid)

The human genome

Finally mapped
About 30.000 genes
About 85.000 mRNAs

Nucleus
DNA gene chromosome

RNA cytosol produce proteins

mRNA (messenger RNA)
tRNA (transfer RNA)
rRNA (ribosomal RNA)

DNA & RNA

Information stored in DNA and RNA direct
the synthesis of proteins that determine
the shape and function of a cell

DNA
When DNA is damaged entry into
mitosis is inhibited giving the cell time
to repair
Failure to repair damaged DNA leads to
cancer
The cell cycle is regulated by proteins:
cyclins and cyclin-dependent protein
kinases

Genetic aspect of cancer

Some cancers are caused by oncogenes
genes that are carried in the genomes of cancer
cells and responsible for producing their
malignant properties
Derived by somatic mutation from protooncogenes (normal genes that control growth)
> 100 oncogenes
Another genes produces protein suppress
tumor

Oncogenes
The p53 gene is mutated in up to 50% of
human cancer patients produce p53
proteins fail to slow the cycle cell and
permit other mutation in DNA
The accumulated mutations cause cancer
The BRCA-1 gene breast cancer

Regulation of gene expression

Each nucleated somatic cell full genetic
message great differentiation and
specialization in the functions
Only small part of the message are
normally transcribe normally
maintained in repressed state
gene are controled: spatially &
temporally

Regulation of gene expression

What turns on genes in one cell and not in other
cell
What turns on genes in one cell at one stage of
development ad not at other
What maintains orderly growth in cells and
prevents the uncontrolled growth (cancer)
DNA sequences promotes orderly
transcription of the gene (cis regulation)
transciption factors are product of other gene
mediate trans regulation

Molecular medicine
Antibiotics: inhibit protein synthesis in
bacteria
Antiviral (acyclovir, ganciclovir): inhibit
DNA polymerase

Siklus Kehidupan Sel

Jumlah sel tubuh: 75-100 triliun
Sel hidup dalam fase: - interphase
- mitosis
Pembelahan sel
- Mitosis
- Meiosis
- Sitokinesis

Fase Pembelahan Sel

Fase Mitosis (M phase):
Prophase
Metaphase
Anaphase
Telophase

Periode bermitosis
Sel otot dan sel saraf (long-lived cells)
hampir tidak bermitosis
Sel epitel (kulit, mukosa) dalam hari / jam

Telomeres

Cell replication involve:

- DNA polymerase of chromosomes
- transcriptase: telomeres of
chromosomes telomerase
High telomerase activity ( includes most
cancer cells) keep multiplying
indefinitely

Kehidupan sel
Sel membelah diri sebentar
Sebagian besar hidup sel dalam masa interphase:
- fungsi sel normal fase Go
- persiapan untuk membelah
diri fase G1. S dan G2
Sel otot lurik & sebagian besar neuron Go terus
menerus (tidak pernah membelah diri)
Stem cells membelah diri berulang-ulang tidak
pernah masuk Go

Interphase
Fase G1 (8-12 jam) : sel siap membelah diri,
dibuat cukup mitokondria, sitoskeleton, retikulum
endoplasmik, ribosom, dll.
Fase S (6-8 jam): menduplikat kromosom, al:
replikasi DNA
Fase G2 (2-5 jam) : selesaikan replikasi sentriol
masuk fase M (mitosis)
Fase Go = fase berfungsi normal sangat
bervariasi

Apoptosis
Suatu program kematian sel
Setiap sel punya jalur yang bila diaktifkan
menyebabkan sel bunuh diri dg
menghasilkan ensim protein yang
menghancurkan sel itu.
Peristiwa normal dlm kehidupan

Peran Apoptosis
Bagian normal dari pertumbuhan
Penting pada tissue turnover pd dewasa
Penting pada sistem imun buang sel
yang terinfeksi virus
Membuang sel yang tidak diperlukan /
menghambat homeostasis: sel tua, sel
rusak, sel bermutasi (sebelum menjadi
kanker)

Sitokin (cytokines)
= hormon lokal, paracrine factors
Chemical messenger yg dilepaskan sel
untuk koordinasi aktivitas lokal
Diproduksi banyak sel untuk komunikasi
parakrin, komunikasi sel ke sel dalam satu
jaringan.
Yg diproduksi sel pertahanan kerja spt
hormon
Contoh: interferron, prostaglandin

Prostaglandin
Dihasilkan sel tertentu
Efek utama pada jaringan setempat
Efek sekunder pada jaringan / organ lain
seperti hormon

Hormon
Chemical messenger yang dilepaskan
pada satu jaringan, masuk aliran darah
sel spesifik pada jaringan lain

Extracellular chemical messenger

Parakrin
Neurotransmiter
Hormon
Neurohormon

Chemical messenger
First messenger : berikatan dg reseptor
respon intrasel
- buka / tutup pintu spesifik
- transfer sinyal ke chemical messenger
intrasel (second messenger )
Second messenger : mencetuskan serial
biokimiawi dlm sel
transduksi sinyal

Transduksi Sinyal
Dicetuskan oleh ikatan chemical
messenger pd reseptor
Tujuan: - fungsi
- pertumbuhan
- survival
- replikasi (reproduksi sel)

Membrane channels
Leak channels : selalu terbuka
Gated channels : terbuka / tertutup oleh
stimulus

Gated channels
Chemical messenger berikatan dg
reseptor membran spesifik
Mengubah kelistrikan membran sel
Deformasi mekanik pd channels

cAMP & cGMP

Suatu second messenger
Rangsang reseptor protein G
adenil siklase cAMP & cGMP
aktifkan protein kinase fosforilasi
protein sel > aktif
Dihidrolisis oleh PDE (phosphodiesterase)

Modifications of second messenger pathways

Jumlah reseptor
Afinitas reseptor

Reseptor sel
Terdapat pada:

membran sel
sitoplasma
nukleus

Reseptor Membran Plasma

Terutama untuk menangkap ligand
Ligand : - hormon
- neurotransmiter
- antigen
- komplemen
- lipoprotein
- mikroba infeksi
-obat
- metabolit

Reseptor Adrenergik
Terdapat pada dinding sel target
Reseptor 1 dan 2
Reseptor 1 dan 2
Reseptor > sensitif thd norepinefrin
Reseptor 1 sama sensitif epi norepi
Reseptor 2 > sensitif thd epinefrin
Obat: blocker
blocker
2 agonist

Reseptor Adrenergik:
1 : dilatasi pupil , konstriksi arteriol
2 : kontraksi otot saluran cerna
1 : denyut jantung:
2 : saluran napas: dilatasi

Reseptor obat

Anestetika
Opiat
Endorfin
Enkefalin
Antibiotik
Kemoterapi kanker
Digitalis

Reseptor mikroba
Mengikat : bakteri, virus dan parasit
Reseptor antigen pada limfosit dll:
mengenal dan mengikat antigen
mengaktifkan respon imun dan inflamasi

Reseptor Endorfin
Endorfin = opiate like peptide dari
kelenjar hipofisa
Reseptor sangat banyak terdapat pada
jalur saraf penghantar rasa nyeri
Reseptor + opiat perubahan
permeabilitas membran modulasi rasa
nyeri

Penyakit
Diabetes melitus: jumlah reseptor insulin
sbg respon thd elevasi kronik insulin dlm
darah
Myasthenia gravis: reseptor asetilkolin
rusak
Kolera: toksin kuman menghambat
inaktivasi cAMP pada sel dinding usus.
cAMP merangsang sekresi cairan ke
lumen

Growth factors
Polypeptides / proteins
One group:
- insulin-like growth factors
- nerve growth factors
- activins
- inhibins
Second group: Cytokines
Colony-stimulating favtors regulate
proliferation and maturatin and maturation of red
and wihte

Hypercalcemia of malignancy
Cause by bone metastases
Produce by PGE from the tumor
Also by circulating PTH (humoral
hypercalcemia of malignancy)

Hormones & Cancer

Estrogen-dependent breast carcinoma
Often have a remission when their ovaries
removed
Tamoxifen: inhibit the action of estrogens
remission
Ca prostate androgen-dependent