14 nots - 1 Lecture 14 October 29, 2008 Integrin-regulated...

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Lecture 14 October 29, 2008 Integrin-regulated FAK-Src and integrin linked kinase signaling: focal adhesion, cell motility, and chondrogenesis. Text was taken verbatim from the cited textbook and research publications. Alberts, Molecular Biology of the Cell, 4th Ed and Lodish Molecular Cell Biology 4th Edition Activation of the FAK-Src complex and cell motility Before examining how integrins promote cell migration via the activation of the FAK-Src complex, it is necessary to re-examine some topics covered in BIO250: the molecular basis of actin-myosin contractions in non-muscle cells, the activation of small monomeric GTPases, and the hierarchy of focal contacts between integrins and ECM molecules. Actinomyosin contractions in non-muscle cells Myosin Motors While actin polymerization can push plasma membranes to generate cellular protrusions at the leading edge, movement of cells is also dependent on the interaction of actin cytoskeleton with myosin motors. Myosin motors move along actin filament by hydrolysis of ATP to transform chemical energy into mechanical energy- hence myosin motors are often referred to as mechanochemical motors . Alberts, 4th edition, gives a description of the several members of the myosin family. The focused of the course is on myosin I and myosin II as they play key roles in promoting cellular movements. See figure 18-20 for a schematic of myosin motors. The tail domain determines specific functions of the motors. The tail of myosin I interacts with lipid bilayers, by a still poorly understood mechanism. Via its interactions with the plasma membrane and actin- filaments at the leading edge of migrating cells, it’s hypothesized that myosin I promotes lamellipodia and filopodia extensions. Myosin II, in a manner similar to its role in sarcomere contractions in muscle cells, promotes contraction of stress fibers and the formation of focal adhesion. A property exhibited by all moving cells is polarity; that is, certain structures always form at the front of the cell, whereas others are found at the rear. Cell migration is initiated by the formation of a large, broad membrane protrusion at the leading edge of a cell. Video microscopy reveals that a major feature of this movement is the polymerization of actin at the membrane. In addition, actin filaments at the leading edge are rapidly cross-linked into bundles and networks in a protruding region, called a lamellipodia in vertebrate cells. In some cases, slender, fingerlike membrane projections, called filopodia, are also extended from the leading edge. These structures then form stable contacts with the underlying surface and prevent the membrane form retracting. (In some cases, filopodia act like antennae, promoting retraction). Actin dynamics and force generation by myosin II motors
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This note was uploaded on 09/29/2009 for the course CSB csb327 taught by Professor Ringuitte during the Fall '08 term at University of Toronto- Toronto.

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14 nots - 1 Lecture 14 October 29, 2008 Integrin-regulated...

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