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Dr.DWI WINARNI, M.Si Dept. Biologi FSaintek Univ. Airlangga Biologi Sel - pertemuan IV.

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Presentasi berjudul: "Dr.DWI WINARNI, M.Si Dept. Biologi FSaintek Univ. Airlangga Biologi Sel - pertemuan IV."— Transcript presentasi:

1 Dr.DWI WINARNI, M.Si Dept. Biologi FSaintek Univ. Airlangga Biologi Sel - pertemuan IV

2 biosel_S1_bio SEL HIDUP Non SELULAR (ECM) Non SELULAR (ECM) SELULAR LINGKUNGAN INTERAKSI Komponen permukaan sel MENENTUKAN BENTUK/JENIS Ligan terlarut ( soluble ligand ) Hormon, growth factor Ligan terlarut ( soluble ligand ) Hormon, growth factor Matriks ekstrasel ( fixed ligand ) Matriks ekstrasel ( fixed ligand )

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4 YANG BERPERAN DALAM INTERAKSI SEL DENGAN LINGKUNGANNYA

5 biosel_S1_bio Merupakan kelompok protein integral membran yang terdapat pada permukaan sel vertebrata Tersusun atas 2 rantai polipeptida, 1 rantai  dan 1 rantai  yang terangkai secara nonkovalen  16 jenis rantai   8 jenis rantai  22 heterodimer

6 biosel_S1_bio Rantai  meningkatkan spesifitas pengikatan ligan

7 biosel_S1_bio 1. ADESI SEL PADA SUBSTRAT/ SEL 2. TRANSMISI SINYAL DARI EKSTRASEL (outside-in signaling) 2. TRANSMISI SINYAL DARI EKSTRASEL (outside-in signaling)

8 biosel_S1_bio 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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10 Jenis reseptor DistribusiJenis ligan  Sel T teraktivasi, timosit, endotel, fibroblas, epitel, astrosit Fibronektin  Sel T dan B teraktivasi, sel T memori, timosit, fibroblas, epitel, platelets, astrosit, endotel Fibronektin    b   Sel T dan B teraktivasi, sel T memori, timosit, fibroblas, epitel, platelets, endotel Fibronektin Vitronektin Fibrinogen Von Willebbrand factor vv Fibroblas, monosit, makrofag, epitel, sel tumor Vitronektin BEBERAPA JENIS RESEPTOR INTEGRIN DAN JENIS LIGAN YANG DIKENAL MELALUI SEKUENS RGD

11 biosel_S1_bio Jenis reseptor integrin DistribusiJenis ligan  NKC, sel T dan B teraktivasi, fibroblas, sel glia, perinerium, sel Schwann, sel ependim Kolagen  NKC, sel T dan B teraktivasi, platelet, endotel, epitel, astrosit, fibroblas, sel Schwann, sel ependim Kolagen Laminin  Sel T dan B teraktivasi, timosit, endotel, fibroblas, epitel, astrosit Kolagen Laminin 44 NKC, sel T dan B teraktivasi, eosinofil, endotel, otot, fibroblas Fibronectin VCAM BEBERAPA JENIS RESEPTOR INTEGRIN DAN JENIS LIGAN YANG DIKENAL MELALUI SEKUENS nonRGD

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13 INTEGRIN MENGIKATKAN SEL PADA SUBSTRAT

14 biosel_S1_bio Sel dalam biakan secara diskrit mengadakan perlekatan pada permukaan. Kontak integrin (  5  1) 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 FOCAL CONTACT / FOCAL ADHESIONS

15 biosel_S1_bio LM= laminin

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18 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

19 biosel_S1_bio HEMIDESMOSOM

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21 Sel dapat mengekspresikan berbagai jenis integrin pada permukaannya Sel dapat mengikat berbagai jenis komponen matriks ekstraselular

22 Sel-sel basal mengekspresikan integrin  dan  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)

23 biosel_S1_bio 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  atau  integrin atau laminin  bula (termasuk pada dinding saluran gastrointestinal dan urin)

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31 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

32 biosel_S1_bio SELECTINS E-SELECTINS CD62e E-SELECTINS CD62e P-SELECTINS CD62p P-SELECTINS CD62p L-SELECTINS CD62l L-SELECTINS CD62l SEL-SEL ENDOTEL PLATELETS ENDOTEL PLATELETS ENDOTEL SEMUA JENIS LEKOSIT

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34 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

35 biosel_S1_bio At sites of inflammation, neutrophils and monocytes, or neutrophil- or monocyte- derived 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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41 A schematic of the structure of the T-cell receptor (TCR)

42 Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells

43 biosel_S1_bio 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 of atopy.

44 biosel_S1_bio 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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47 biosel_S1_bio - 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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50 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 Peran chaderin dalam morfogenesis

51 biosel_S1_bio Cell sorting owing to differential expression of cadherins drives tissue separation during embryonic development. Expression of N- cadherin (neural cadherin; blue) in the presumptive neural epithelium allows it to separate from the E-cadherin-expressing ectoderm (yellow)

52 biosel_S1_bio 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.

53 biosel_S1_bio 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

54 biosel_S1_bio 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

55 biosel_S1_bio Cell migration. In contrast to its role in stabilizing epithelial junctions, E- cadherin 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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