Komponen Permukaan Sel Biologi Sel - pertemuan IV Komponen Permukaan Sel Dr.DWI WINARNI, M.Si Dept. Biologi FSaintek Univ. Airlangga biosel_bio_s1

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

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Komponen permukaan sel YANG BERPERAN DALAM INTERAKSI SEL DENGAN LINGKUNGANNYA 1. INTEGRINS 2.SELECTINS 3. IMMUNOGLOBULINS superfamily 4. CADHERINS biosel_S1_bio

1. INTEGRIN 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 8 jenis rantai b 22 heterodimer biosel_S1_bio

Rantai a meningkatkan spesifitas pengikatan ligan biosel_S1_bio

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

ASAM AMINO arginin-glisin-asam aspartat (nomenklatur baru= RGD), 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+ biosel_S1_bio

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Jenis reseptor Distribusi Jenis ligan 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 a11bb3 Sel T dan B teraktivasi, sel T memori, timosit, fibroblas, epitel, platelets, endotel Vitronektin Fibrinogen Von Willebbrand factor avb5 Fibroblas, monosit, makrofag, epitel, sel tumor biosel_S1_bio

Jenis reseptor integrin 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 Laminin a3b1 Sel T dan B teraktivasi, timosit, endotel, fibroblas, epitel, astrosit a4b1 NKC, sel T dan B teraktivasi, eosinofil, endotel, otot, fibroblas Fibronectin VCAM biosel_S1_bio

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INTEGRIN MENGIKATKAN SEL PADA SUBSTRAT biosel_S1_bio

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 biosel_S1_bio

LM= laminin biosel_S1_bio

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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 biosel_S1_bio

HEMIDESMOSOM biosel_S1_bio

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Sel dapat mengekspresikan berbagai jenis integrin pada permukaannya Sel dapat mengikat berbagai jenis komponen matriks ekstraselular biosel_S1_bio

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) Sel-sel basal mengekspresikan integrin a2b1, a3b1 dan a5b1 yang berperan dalam ikatan desmosom dengan komponen membrana basalis

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 gastrointestinal dan urin) biosel_S1_bio

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2. SELEKTIN (selectinS) 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 biosel_S1_bio

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

Lymphocytes homing biosel_S1_bio

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 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. biosel_S1_bio

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3. Immunoglobulin superfamily biosel_S1_bio

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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 of atopy. 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 biosel_S1_bio

4. CADHERINS 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) biosel_S1_bio

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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 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) 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. biosel_S1_bio

Formation of compartment boundaries 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 biosel_S1_bio

Growth cone motility and synapse formation 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 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. biosel_S1_bio

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