CSB327 - Lecture 1.docx

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Department
Cell and Systems Biology
Course
CSB327H1
Professor
Maurice Ringuette
Semester
Fall

Description
CSB 327 – Lecture 1 Two Types of Extracellular Matrices 1) Basal Lamina/Basement Membranes – Thin sheet like ECM where epithelial cells rest, BL also surrounds muscle and adipose cells and peripheral nerves 2) Connective Tissue ECM –most abundant, majority of CT = interstitial matrices, almost all ECM are represented by CT a. Can sometimes contain solitary cells, while main source of ECM in CT = fibroblasts b. Contains fibroblasts, macrophages, collagen fibres, capillaries (vascularisation), glycoproteins, elastic fibres (e.g. elastin), hyaluronan, proteoglycans Order of layers (from top down)  epithelium  BL  CT - Epithelial cells are aware of connective tissue env. bc of basal lamina which communicates the environment to the cell - Loss of contact bw epithelial cell/BL/CT often causes blistering diseases via immunological responses - Matrisome = 300 ECM coding genes Introduction & Overview of ECMs and Fibril-forming Collagens - Tissue fibrosis = overproduction of collagen = harder tissues; bad for some organs e.g. don’t want heart to become more rigid/fibrotic - ECM proteins consist of collagens, proteoglycans, glycoproteins  found in all tissues o non-collagenous structural proteins are also a ECM protein (e.g. elastin, lamprin, egg shell proteins) but is mainly found in connective tissues Diverse Structural and Regulatory Functions of ECMs - In addition to forming 3d scaffolds /w complex biomechanical properties, ECMs have diverse regulatory fcns that affect the cell - Over time subset of CT can remodel quickly but under diff tensional forces the remodelling process may not bring CT back to original form - One of the key themes of the course: dynamic reciprocity/cross-talk of ECM: o ECM have structural and regulatory activities critical for the development of multicellular organisms o What cells secrete in turn affects their bio activities that in turn lead to further changes in activity of surrounding cells o Post-gastrulation a lot of cross-talk is occurring, as ECM is laid down during embryogenesis ECM made feeds back to change cellular genetic activity which then makes proteins which can remodel ECM already made  dynamic process of laying down ECM, then remodelling it to fit the needs of the ever changing organism - You do not start to see a basal lamina until the jellyfish  due to decreased cleavage of N-terminus of procollagen (high pN-termini lvls) Examples of Connective Tissue Pathologies associated /w defects in ECM molecules - Achondroplastic dwarfism - Osteogenesis Imperfecta - Ehlers Danlos Syndrome/Joint Hypermobility o Hypermobile joints+paper thin skin are attributed to lack of tensile strength in collagens to maintain their biomechanical properties which makes it easier to pull joints and tendons - Lots of collagen in your heart + vascular system = collagen defect esp. /w aneurysms ECM Molecule Biosynthesis and Secretion - Main pathway: o Nucleus transcription  mRNA  translation arrested /w primary transcript attached to ribosome  ribosome shipped to ER  ECM translated in ER  shipped to golgi via secretory vesicles  travels through golgi and out of PM of the cell - How does a cell decide which proteins are destined to be translated in the cytoplasm or in the ER?  molecules capable of self-assmebly like collagens do not want to be kept in cytosol o Translation begins in the cytosol /w N-terminus always being made first o When ~70 AA have been polymerized the signal peptide is no longer masked by the ribosome and is revealed in nascent protein  Signal peptide features 1+ basic AA residues followed by continuous stretch of 6-30 neutral, hydrophobic, and small AA  Basic AA include Arg, Lys  Neutral, hydrophobic, small AA = Ala, Ile, Gly, Leu, Val, Thr, etc - How ER signal sequences and SRP direct ribosomes to the ER membrane. o The SRP binds to both the exposed ER signal sequence and the ribosome, thereby inducing a pause in translation. o The SRP receptor in the ER membrane, which is composed of two different polypeptide chains, binds the SRP–ribosome complex and directs it to the translocator. o The SRP and SRP receptor are then released, leaving the ribosome bound to the
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