MED105 Medical Biology: Cell Surface Modifications PDF

MED105 MEDICAL BIOLOGY SPECIALIZATIONS OF THE CELL SURFACE (CELL SURFACE MODIFICATIONS) Asst. Prof. Fulya Küçükcankurt Department of Medical Biology e-mail: [email protected] Levels of organization in a multicellular organism Tissues are organized into fo...

MED105 MEDICAL BIOLOGY SPECIALIZATIONS OF THE CELL SURFACE (CELL SURFACE MODIFICATIONS) Asst. Prof. Fulya Küçükcankurt Department of Medical Biology e-mail: [email protected] Levels of organization in a multicellular organism Tissues are organized into four broad categories based on structural and functional similarities Types of tissue: 1. Connective tissue 2. Epithelial tissue 3. Muscle tissue 4. Nervous tissue Epithelial cells are the building blocks of epithelial tissue  There are several different types of epithelial cells based on their shape and arrangement Surface epithelium is classified by: Number of layers Simple: one layer Pseudostratified: one layer, but appears to have several layers Stratified: multiple layers Shape of cells at surface Squamous: heightwidth Cell Surface Modifications Specializations of the cell surface, mediating various functions Provide transportation Provide movement Connecting the cells to each other 1)Apical domain specializations: Microvilli Cell Surface Modifications Stereocilia Cilia Flagellum 2)Lateral domain specializations: Cell-to-cell junctions: a)Occluding: tight junctions b)Anchoring: Zonulae adherentes Fasciae adherentes (only in cardiac muscle cells) Desmosomes c)Communicating: gap junctions 3)Basal domain specializations: Basement membrane Cell-to-extracellular matrix (ECM) junctions: Anchoring: Focal adhesions Hemidesmosomes  The cells make up ephitelium have 3 principal characteristics: Cell junctions Polarity Basement membrane Special characteristics of Ephitelial Cells Polarity:epithelial tissues always have an apical and basal surface Support by connective tissue:at the basal surface, both the epithelial tissue and the connective tissue contribute to the basement membrane Cellularity:cells are in close contact with each other with little or no intercellular space between them Junctional Complex:for both attachment and communication  Cell Polarity is a main feature of many types of cells Epithelial cells show polar differentiation They have apical, lateral and basal sufaces They exibit modifications on their surfaces  Apical surface is located on the side of the lumen, or external environment. This pole show apical membrane specializations which alter the shape of this surface Lateral surfaces is on the sides and typically allows for connections with neighboring cells. Basal surfaces is the bottom edge of the cell and is adjacent to the basal lamina of the extracellular matrix, which separates the epithelial cell from the surrounding connective tissue. Cell form, structure, and function variations inside a cell are referred to as cell polarity. APICAL SURFACE MODIFICATIONS The surface of the most cells have extensions They are used in cell movement, absorbtion. Three types of specializations Microvilli Cilia, flagella Stereocilia  I- SPECIALIZATIONS OF FREE SURFACE (APICAL SURFACE ) 1-Microvilli surface extensions that increase surface area Specialized for absorption (15-40x in intestinal tract, kidneys); sensory (taste buds, inner ear) Brush border= dense ‘fringe’ (mucus membrane) 2-Cilia, flagella hairlike projections, nonmotile (more common) & motile (respiratory tract & uterine tubes) Beat in waves to sweep mucus, oocyte, embryo Beat in cell surface 3-Stereocilia whiplike structure much longer than cilia tail of sperm  Transmission electron micrograph of microvilli at the apical 1-Microvilli surfaces of proximal tubule epithelial cells. Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine pp 1116–1121 Finger-like projections from the cell surface (size: 0.1 μm width and 1–3 μm long) Functions: 1. Increase the surface area for diffusion and minimize any increase in volume 2. Cellular adhesion 3. Mechanotransduction 4. Absorption 5. Secretion The specific localization on microvilli of important functional membrane proteins such as glucose transporters, ion channels, ion pumps, and ion exchangers indicate the importance and diversity of microvillar functions Scanning electron microscopy micrograph showing microvilli that protrude from the cell surface of resting peripheral blood human T cells. Frontiers in Immunology-2020 Microvillus Structure Microvilli are made up of 5 main proteins: actin, fimbrin, villin, myosin (Myo1A), calmodulin Actin filaments are cross linked into closely packed bundles by actin bundling proteins; fimbrin villin Actin filaments are attached to the plasma membrane by lateral arms consisting of myosin I calmodulin Animation:Microvilli 2-Cilia and Flagella Cilia and flagella are microtubule-based projections of the plasma membrane Cilia act as antennae that sense a variety of extracellular signals as well as being responsible for movement. There are 2 types of eukaryotic cilia, called primary (non- motile) cilia and motile cilia. Primary (non-motile) cilia are found on most animal cells and are involved in sensing extracellular signals, including movement, odorants, and light. Motile cilia are responsible for cell movement Cilia Light microscope Scanning electron microscope SEM  Cilia Classification 1)Motile cilia (flagella): Mechanical function. It is also found in single-celled organisms. In humans: - Airways cleaning - Sperm motility Motile cilia in respiratory tract - Conduction of the ovum from the fallopian tubes to the uterus - Ependymal cells in the choroid plexus located in the ventricles of the brain (CSF circulation!) 2)Non-motile (primary): They exist in multicellular organisms and function as "sensors". -They are found in almost every cell in humans. Primary cilia arising from a neuron  Motile Cilia 1-Surface of epithelial cells of the upper respiratory tract 2- Epithelial cells of the uterine tubes (oviducts ) 3- Epithelial cells of the efferent ducts (Ductus efferentes) The efferent ducts connect the testis with the epididymis. Uterine tubes (oviduct) Efferent ducts Respiratory tract Motile Cilia Functions 1-To move mucus over epithelial surfaces in respiratory epithelium toward the mouth. (Clear the mucus together with dust particles, dead cells and bacteria from respiratory passages) 2- In uterine tubes to transport the ovum toward the uterus. 3- In ductus efferentes (efferent ducts) to propel the spermatozoa toward the epididymis Uterine tubes (oviduct) Efferent ducts Respiratory tract The ciliated cells of the fallopian tube play a major role: transport of the ovum, the sperm cells and the zygote (a fertilized ovum)  Cells 2022, 11(9), 1416 The ciliated cells are located across the apical surface and facilitate the movement of mucus across the airway tract. Cilia cells : Move back and forth, carrying mucus up and out of the respiratory tract Non-Motile (Primer) Cilia Functions Developmental signaling pathways Wnt, Hedhehog Growth and differentiation Transforming growth factor β Platelet derived growth factor Sensory Photoreceptors, olfactory receptors Hormonal regulation MChr1 (Melanin-concentrating hormone receptor 1), 5HTr6 (5-Hydroxytryptamine (Serotonin) Receptor 6) Mechanical detection PCD1, PCD2 Two different sensory receptor cells have active transport systems served by their primary cilia Nature Reviews Genetics 6, 928–940 Basic Cilia Structure 1-Axoneme 2-Cell membrane 3-IFT (Intraflagellar Transport) 4-Basal body (derived from Centriole) 5- Cross section of the cilium 6- Microtubule triplets in basal body  Structures of primary (non-motile) and motile cilia Both non-motile and motile cilia are anchored in a centriole called a basal body, which contains nine triplets of microtubules 9+2 axoneme 9+0 axoneme Two of the microtubules in each triplet of the basal body are extended to form the axoneme. Diagram of ciliary structure Nature 448, 638–641 In each doublet ; Microtubule A is complete, it consist of 13 protofilaments in its wall (it has «O» shaped cross section) Microtubule B is incomplete, it consist of 10- 11 protofilament, it has a C shaped cross section. It is fused to Microtubule A and closes the defect in its Wall. Dynein arms Arranged along the length of the microtubule They are formed by a protein called dynein and contain ATPase (ATP splitting enzyme) activity. Nexin links Nexin links attach each microtubule A to the microtubule B of the adjacent doublet. ▪ Nexin links are composed of an elastic material called “nexin’’ ▪Nexin is the interdoublet link protein responsible for the maintenance of the nine-fold configuration in cilia and flagella. ▪ Responsible for recovery stroke (backward movement) MECHANISM OF CILIARY MOVEMENT Sliding Microtubule Mechanism The bending of an axoneme (A) When axonemes are exposed to the proteolytic enzyme trypsin, the linkages holding neighboring doublet microtubules together are broken. In this case, the addition of ATP allows the motor action of the dynein heads to slide one pair of doublet microtubules against the other pair. (B) In an intact axoneme (such as in a sperm), sliding of the doublet microtubules is prevented by flexible protein links. The motor action therefore causes a bending motion, creating waves or beating motions, Movement of Motile Cilia and Flagella Ciliary and flagellar movements are generated by microtubule sliding with axonemal dynein motors. Cilia and flagella are Cytoskeleton made up of microtubules. Movement= nine paired microtubule sets of the axoneme slide against one another causing cilia and flagella to bend. The motor protein dynein is responsible for generating the force required for movement. Ciliopathy Defects in ciliary activity cause a number of diseases Motile Ciliopathy: Immotile cilia syndrome, primary ciliary dyskinesia 1- Male infertility Normal number of spermatozoa but no motility 2- Respiratory tract disorders -Bronchiectasis (chronic dilation of bronchi ) -Chronic sinusitis 3-Situs inversus (complete transposition (right to left reversal) of the thoracic and abdominal organs Heart being in right, liver being in left The “gold-standard” diagnostic test for PCD has been electron microscopic Axial CT image showing situs inversus ultrastructural analysis of respiratory cilia obtained by nasal scrape or bronchial The liver is normally on the right side of the body and the spleen on the left, they are brush biopsy. switched in this patient with situs inversus. KARTAGENER SYNDROME  Electron Microscopic observation of immotile sperm flagellum of patients with Kartagener’s syndrome: Showed the absence of dynein arms Electrone microscope observation of bronchial biopsies showed no dynein arms in ciliary axonemes Dynein is essential for motility of cilia and flagella Kartagener syndrome is a genetic disease There is a congenital defect in the synthesis of dynein 1. Normal 2. Absent inner and outer dynein 3. Absent outer dynein 4. Absent inner dynein Genetics in Medicine volume 11, pages473–487 FLAGELLA Flagellum propels sperm 1- Longer than cilia Longest flagella are those of mammalian sperm 2- Same internal structure with cilia (Axoneme 9+2 ) 3-Different type of movement (undulating wave type of movement) Mammalian spermatozoa and flagellum structure 4- Less in number (one or two in a single cell) 5- Mammalian spermium contains 9 additional dense fibers arround the axoneme (9+9+2) (protective function) Scanning electron micrograph of a human sperm contacting a hamster egg. Stereocilia 1. Non-motile apical cell modifications 2. Long and irregular microvilli 3. Have no microtubule containing internal structure 4. Contain actin, lack of axoneme Bechara Kachar,NIH Localisations: epididymis, vas deferense, sensory of the inner ear Stereo cilia are found in the male reproductive tract and are thought to facilitate absorption in the epididymis and vas deferens. Stereocilia are essential in hearing and balance in inner ear.  Sensory cells in the inner ear The apical side of the inner ear hair cell carries the highly organized, actin-filled stereocilia Mechanotransduction function The stereocilia are anchored in the actin-rich cuticular plate. The kinocilium is located lateral to the largest stereocilium and is formed from the basal body. Damage to these cells results in decreased hearing sensitivity and balancing Stereocilia in male reproductive system In epididiymis, pseudostratified epithelium whose cells contain non-motile stereocilia. These stereocilia absorb much of the excess fluid containing the spermatozoa. The vas deferens is lined by a pseudostratified columnar epithelium composed of columnar cells and basal cells. The luminal surface of the columnar cell is lined by stereocilia. Epididymis Vas deferense