08_14_lecture.pptx

Chapter 14 Cellular Movement: Motility and Contractility Lectures by Kathleen Fitzpatrick © 2016 Pearson Education, Inc. Simon Fraser University Cellular Movement: Motility and Contractility  Cell motility involves  Movement of a cell or organism through the environment  Movement of the enviro...

Chapter 14 Cellular Movement: Motility and Contractility Lectures by Kathleen Fitzpatrick © 2016 Pearson Education, Inc. Simon Fraser University Cellular Movement: Motility and Contractility  Cell motility involves  Movement of a cell or organism through the environment  Movement of the environment past or through a cell  Movement of components in the cell  Contractility, is the shortening of muscle cells, a specialized form of motility © 2016 Pearson Education, Inc. Motile Systems  Intracellular movement  Microtubules play a role in the separation of chromosomes during cell division  To generate movement, microtubules (MTs) and microfilaments (MFs) provide a scaffold for motor proteins that produce motion at the molecular level  microtubules and microfilaments are the roads  motor proteins are the cars © 2016 Pearson Education, Inc. Two Eukaryotic Motility Systems 1. Microtubule-based motility  Examples: fast axonal transport in neurons; the sliding of MTs in cilia and flagella 2. Microfilament-based motility  Example: muscle contraction © 2016 Pearson Education, Inc. Molecular Motors: Common Features  Couple ATP hydrolysis to changes in shape & addition of the motor protein  Undergo cycles of ATP hydrolysis, ADP release, and acquisition of new ATP  Move along a cytoskeletal filament for long distances © 2016 Pearson Education, Inc. 14.1 Microtubule-Based Movement Inside Cells: Kinesins and Dyneins  Microtubules provide a set of tracks for transport of a variety of organelles and vesicles  Traffic toward the minus ends is called “inbound”  Traffic toward the plus ends is called “outbound”  Microtubule-associated motor proteins—kinesins and dyneins—walk along the MTs and provide the force needed for movement © 2016 Pearson Education, Inc. Motor Proteins Move Cargoes Along MTs During Axonal Transport  Proteins produced in the cell body are transported to the nerve ending at rates of about 2 μm/sec in a process called fast axonal transport  This involves packaging of these proteins into vesicles for transport © 2016 Pearson Education, Inc. Classic Kinesins Move Toward the Plus Ends of Microtubules  Kinesin is involved in ATP-dependent transport toward the plus ends (away from the centrosome)  Kinesins consist of two dimerized heavy chains and two light chains  The heavy chains contain globular domains that attach to microtubules, a coiled-coil stalk, a lever-like neck that connects the two, and a tail  The light chains are associated with the tail © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. Kinesin Movement Along MTs  Kinesin movement looks like “walking,” the two globular head domains taking turns as the front foot  It can move long distances by releasing bound ADP and acquiring a new ATP, so that the cycle repeats © 2016 Pearson Education, Inc. Kinesins Are a Large Family of Proteins  Kinesins are classified into families based on their amino acid sequence  Some form homodimers; others, heterodimers  Kinesin-14 is minus-end directed; kinesin-5 is bidirectional  The kinesin-13 family, the catastrophins, aid depolymerization of MTs © 2016 Pearson Education, Inc. Dyneins Are Found in Axonmes and the Cytosol  Cytoplasmic dynein moves cargo toward the minus ends  2 types of cytoplasmic dynein have been identified  Protein complexes called dynactin, help link dynein to cargo © 2016 Pearson Education, Inc. Microtubule Motors Direct Vesicle Transport and Shape the Endomembrane System  MT motors are important for dynamically shaping the endomembrane system  Example: membrane extensions of ER can be moved along MTs  The vesicles to and from the Golgi complex are carried by MT motors © 2016 Pearson Education, Inc. 14.2 Microtubule-Based Motility: Cilia and Flagella  Cilia are about 2–10 μm long & occur in large numbers on the surface of ciliated cells  Cilia display an oarlike pattern of beating, generating a force parallel to the cell surface  Unicellular & multicellular eukaryotes © 2016 Pearson Education, Inc. Cilia and Flagella  Flagella move cells through a fluid environment  They are the same diameter as cilia, but usually much longer (up to 200 μm)  Limited to one or a few per cell and move with a propagated bending motion. Generates a force parallel to the flagellum © 2016 Pearson Education, Inc. Cilia and Flagella Consist of an Axoneme Connected to a Basal Body  Cilia and flagella share a common structure, the axoneme  It is connected to a basal body and surrounded by an extension of the cell membrane  Between the axoneme and basal body is a transition zone in which the MTs take on the pattern characteristic of the axoneme © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. Doublet Sliding Within the Axoneme Causes Cilia and Flagella to Bend  The overall length of MT doublets in cilia and flagella does not change during beating  Instead, adjacent outer doublets slide relative to one another  The sliding movement is converted to localized bending © 2016 Pearson Education, Inc. Crosslinks and Spokes Are Responsible for Bending  Radial and circumferential connections restrain sliding and lead to bending  Cleavage of nexin linkages, followed by treatment with ATP, causes doublets to slide past each other  When the linkages are left intact, the axoneme bends when treated with ATP © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. 14.3 Microfilament-Based Movement Inside Cells: Myosins  ATP-dependent motors, the large superfamily called myosins, interact with and exert force on actin microfilaments  Currently there are 24 known classes of myosins © 2016 Pearson Education, Inc. The Myosins  All have at least one heavy chain, with a globular head group attached to a tail of varying length  The globular domains binds actin and uses ATP hydrolysis for energy to move along the actin filament  Most myosins move to the plus end. Myosin VI is an exception © 2016 Pearson Education, Inc. Myosin Functions  Myosins function in a wide range of cellular events, including  Muscle contraction  Cell movement  Phagocytosis  Vesicle transport © 2016 Pearson Education, Inc. Type II Myosins  Type II myosins are the best understood  They have two heavy chains, each with a globular head, a hinge region, and a rodlike tail  In myosin II, one essential light chain and one regulatory light chain are associated with each heavy chain  The basic function of myosin II is to pull arrays of actin filaments together, resulting in contraction of a cell or group of cells © 2016 Pearson Education, Inc. 14.4 Microfilament-Based Motility: Muscle Cells in Action  Muscle contraction is the most familiar example of mechanical work mediated by intracellular filaments  Mammals have skeletal, cardiac, and smooth muscle © 2016 Pearson Education, Inc. Skeletal Muscle Cells Contain Thin and Thick Filaments  Skeletal muscles are responsible for voluntary movement  A muscle consists of parallel muscle fibers joined by tendons to the bones that the muscles move  Each fiber is a long, thin, highly specialized, multinucleate cell © 2016 Pearson Education, Inc. Structure of Skeletal Muscle Cells  Each muscle fiber contains numerous myofibrils, each of which is divided along its length into repeating units called sarcomeres  Each sarcomere contains bundles of thin filaments (containing actin, troponin, and tropomyosin) and thick filaments (containing myosin) © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. Striated Muscle  The filaments in skeletal muscle are aligned, giving myofibrils a pattern of alternating dark and light bands  Dark bands are A bands, and light bands are I bands © 2016 Pearson Education, Inc. Sarcomeres Contain Ordered Arrays of Actin, Myosin, and Accessory Proteins  The arrangement of thin and thick filaments in myofibrils gives rise to  The striated pattern of skeletal muscle  The observed shortening of sarcomeres during contraction © 2016 Pearson Education, Inc. Thick Filaments  Each thick filament consists of hundreds of molecules of myosin  oriented in opposite directions in the two halves of the filament  The myosin is arranged in staggered fashion  Protruding heads of myosin molecules contact the adjacent thin filaments, forming cross-bridges © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. Thin Filaments  Thin filaments interdigitate with the thick filaments  Thin filaments contain three proteins: F-actin, intertwined with tropomyosin and troponin  One troponin complex associates with each tropomyosin  Together they constitute a calcium-sensitive switch that activates contraction in striated muscle © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. The Sliding-Filament Model Explains Muscle Contraction  The sliding filament model was proposed in 1954  According to the model, muscle contraction is due to thin filaments sliding past thick filaments, with no change in length of either © 2016 Pearson Education, Inc.