Download SELULAR LINGKUNGAN INTERAKSI Komponen permukaan sel

Biologi Sel - pertemuan IV
Dr.DWI WINARNI, M.Si
Dept. Biologi
FSaintek Univ. Airlangga
Ligan terlarut
(soluble ligand)
Hormon, growth factor
MENENTUKAN
BENTUK/JENIS
Non
SELULAR
(ECM)
INTERAKSI
SEL
HIDUP
LINGKUNGAN
SELULAR
Komponen permukaan
sel
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Matriks ekstrasel
(fixed ligand)
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YANG BERPERAN DALAM INTERAKSI SEL
DENGAN LINGKUNGANNYA
1. INTEGRINS
2.SELECTINS
3. IMMUNOGLOBULINS
superfamily
4. CADHERINS
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Merupakan kelompok protein integral membran
yang terdapat pada permukaan sel vertebrata
Tersusun atas 2 rantai polipeptida, 1 rantai a dan
1 rantai b yang terangkai secara nonkovalen
16 jenis rantai a
22 heterodimer
 8 jenis rantai b
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Rantai a
meningkatkan
spesifitas
pengikatan ligan
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1. ADESI SEL PADA
SUBSTRAT/ SEL
2. TRANSMISI SINYAL
DARI EKSTRASEL
(outside-in signaling)
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SEBAGIAN BESAR PROTEIN EKSTRASELULAR
BERIKATAN DENGAN INTEGRIN PADA BAGIAN
YANG MENGANDUNG URUTAN (SEKUENS)
ASAM AMINO arginin-glisin-asam aspartat
(nomenklatur baru= RGD),
dengan ligand -binding site tergantung pada
keberadaan ion Ca2+ atau Mg2+
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BEBERAPA JENIS RESEPTOR INTEGRIN DAN JENIS LIGAN YANG
DIKENAL MELALUI SEKUENS RGD
Jenis
reseptor
Distribusi
Jenis ligan
a3b1
Sel T teraktivasi, timosit, endotel,
fibroblas, epitel, astrosit
Fibronektin
a5b1
Sel T dan B teraktivasi, sel T
memori, timosit, fibroblas, epitel,
platelets, astrosit, endotel
Fibronektin
a11bb3
Sel T dan B teraktivasi, sel T
memori, timosit, fibroblas, epitel,
platelets, endotel
Fibronektin
Vitronektin
Fibrinogen
Von Willebbrand factor
avb5
Fibroblas, monosit, makrofag,
epitel, sel tumor
Vitronektin
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BEBERAPA JENIS RESEPTOR INTEGRIN DAN JENIS LIGAN
YANG DIKENAL MELALUI SEKUENS nonRGD
Jenis
reseptor
integrin
Distribusi
Jenis ligan
a1b1
NKC, sel T dan B teraktivasi, fibroblas, sel glia, perinerium,
sel Schwann, sel ependim
Kolagen
a2b1
NKC, sel T dan B teraktivasi, platelet, endotel, epitel,
astrosit, fibroblas, sel Schwann, sel ependim
Kolagen
Laminin
a3b1
Sel T dan B teraktivasi, timosit, endotel, fibroblas, epitel,
astrosit
Kolagen
Laminin
a4b1
NKC, sel T dan B teraktivasi, eosinofil, endotel, otot,
fibroblas
Fibronectin
VCAM
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INTEGRIN MENGIKATKAN SEL PADA SUBSTRAT
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FOCAL CONTACT /
FOCAL ADHESIONS
Sel dalam biakan secara diskrit mengadakan perlekatan pada permukaan. Kontak
integrin (a5b1) dengan protein di substrat yang melapisi permukaan (mis: laminin,
kolagen, fibronektin)  perubahan konformasi integrin sitoplasmik perlekatan
integrin dengan filamen aktin  pengelompokan (clustering) integrin di permukaan
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LM= laminin
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Focal contact merupakan
struktur yang dinamik, yang
setelah terbentuk, secara
cepat akan “terurai” jika sel
dalam biakan terstimulasi
untuk mitosis atau
perubahan organisasi
sitoskeleton yang lain
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HEMIDESMOSOM
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Sel dapat
mengekspresikan
berbagai jenis
integrin pada
permukaannya
Sel dapat mengikat
berbagai jenis
komponen matriks
ekstraselular
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Sel-sel basal mengekspresikan integrin
a2b1, a3b1 dan a5b1 yang berperan
dalam ikatan desmosom dengan
komponen membrana basalis
Sel basal epidermis
merupakan satu-satunya
jenis sel dalam lapisan
epitel epidermis yang
mempunyai kemampuan
membelah, jika sintesis
integrin tidak berhenti saat
sel meninggalkan basal
sel akan terus
membelah kondisi mirip
psoriasis (epidermis
menebal dan mengalami
peradangan)
Bullous pemphigoid
disebabkan oleh terbentuknya autoantibodi terhadap
struktur hemidesmosom  sel epitel bagian basal tidak
dapat melekat pada membrana basalis dan jaringan ikat
di bawahnya  terisi cairan tubuh bula, terutama
nampak pada kulit
Epidermolysis bulosa
disebabkan oleh faktor genetis (perubahan pada protein
penyusun hemodesmosom termasuk subunit a6 atau b4
integrin atau laminin  bula (termasuk pada dinding
saluran gastrointestinalbiosel_S1_bio
dan urin)
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Merupakan kelompok glikoprotein integral
membran yang dapat mengenali dan mengikat
gugus gula tertentu yang terdapat pada
permukaan sel lain
Nama selectin berasal dari lectin yaitu senyawa
yang dapat mengikat gugus gula tertentu secara
spesifik pengikatan selektin pada ligannya
memerlukan ion kalsium
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SELECTINS
E-SELECTINS
CD62e
SEL-SEL
ENDOTEL
P-SELECTINS
CD62p
PLATELETS
ENDOTEL
L-SELECTINS
CD62l
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SEMUA
JENIS
LEKOSIT
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T cell–endothelial-cell interactions as studied in flow chamber systems in
vitro. P-selectin-dependent interactions require functional P-selectin
glycoprotein ligand 1 (PSGL1); E-selectin interactions require poorly defined
E-selectin ligand(s) on activated T cells. L-selectin on T cells interacts with
peripheral node addressin (PNAD). At sites of inflammation, endothelial cells
express P- and E-selectin and during chronic inflammation PNAD is also
expressed by endothelial cells
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At sites of inflammation, neutrophils and monocytes, or neutrophil- or monocytederived microparticles, interact with the inflamed endothelium and present
functional PSGL1 to T cells. This PSGL1 can interact with L-selectin on naive or
central memory T cells. Activated platelets and platelet-derived microparticles are
also known to interact with the vascular endothelium and can present P-selectin to
T cells. Note that for simplicity, not all domains of the selectins are depicted,
although they are represented according
to their relative sizes.
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A schematic of
the structure of
the T-cell
receptor (TCR)
Antigen presentation stimulates T cells to
become either "cytotoxic" CD8+ cells or
"helper" CD4+ cells
The low-affinity IgE receptor, Fc RII (CD23), is expressed by a wide variety of immune
cell types, including B cells and dendritic cells. IgE that is bound to Fc RI or Fc RII
can facilitate allergen uptake by antigen-presenting cells (APCs) and augment
secondary immune responses. b | Most IgE is bound by its high-affinity receptor, Fc
RI, expressed by mast cells and basophils. Crosslinking of IgE bound to Fc RI on
tissue mast cells by specific antigen results in the local release of inflammatory
mediators (for example, histamine and leukotrienes), enzymes and cytokines that
mediate the clinical manifestations biosel_S1_bio
of atopy.
Neural cell adhesion molecule
(NCAM) and L1 have important
roles in cell–cell interactions
through homophilic (NCAM–
NCAM or L1–L1) and
heterophilic (NCAM–L1)
binding. They affect
neurocircuitry (panel b), and, by
interacting with cytoskeletal
components, they can activate
specific intracellular signalling
pathways. These molecules
participate in neurite extension
and guidance, cell
differentiation and survival, and
synaptogenesis. In addition to
their pivotal roles in neural
development and regeneration,
they have been strongly
implicated in synaptic plasticity
and memory formation
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- DITEMUKAN SECARA LUAS DI PERMUKAAN SEL
- UMUMNYA DIMER
- BAGIAN EKSTRASEL MERUPAKAN STRUKTUR TANDEM
BERULANG 5
- BAGIAN INTRASEL BERIKATAN DENGAN PROTEIN SITOPLASMIK
CATENIN CATENIN BERIKATAN DENGAN AKTIN SITOSKELETON
- Jenis:
1. yang berinteraksi dengan sitoskeleton
(Cadherin N, P, R, B, dan E)
2. berasosiasi dengan desmosom (desmoglein, desmocolin)
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Peran chaderin dalam morfogenesis
The epithelial–mesenchymal transition (EMT) and its reverse — the mesenchymal–epithelial
transition. E-cadherin (epithelial cadherin) mediates the adhesion of cells, the transition of cells
from organization in a loose mesenchymal network — in which they lack polarity and have
migratory and invasive potential — to their tight apposition in a polarized epithelial barrier, and
the formation of tight junctional complexes. Loss of E-cadherin expression is associated with
the EMT and its loss or dysregulation plays a part in tumour cell invasion and metastasis. The
yellow cells express E-cadherin,
in contrast to the blue cells that do not
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Cell sorting owing to differential expression of cadherins drives
tissue separation during embryonic development. Expression of Ncadherin (neural cadherin; blue) in the presumptive neural
epithelium allows it to separate from the E-cadherin-expressing
ectoderm (yellow)
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The dynamic breaking and reforming of cadherin adhesive
bonds is required for cells to change neighbours despite being
held together in the tissue. In the example shown, called
convergence and extension, cells rearrange in such a way as to
cause the tissue to narrow and elongate.
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Formation of compartment boundaries. Selective adhesion, which is
accomplished through regulation of adhesive strength, creates
boundaries between developmental compartments in a tissue, as in
the formation of rhombomeres in the developing vertebrate hindbrain
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Growth cone motility and synapse formation. N-cadherin (and
other cadherins) can mediate growth cone motility along cells that
express N-cadherin. Cadherins also form adherens-type junctions
as part of the synaptic junction, which is important for synaptic
specificity, regulation of synaptic plasticity and dendrite
morphogenesis
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Cell migration. In contrast to its role in stabilizing epithelial junctions, Ecadherin also mediates the long-range migration of cells through tissues; for
example, the migration of border cells (pink) in the Drosophila
melanogaster egg chamber. The border cells migrate from one end of the egg
chamber between the nurse cells until they reach the oocyte.
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