CELL SIGNALLING and MEMBRANE TRANSPORT. Mark Louie D. Lopez Department of Biology College of Science Polytechnic University of the Philippines

CELL SIGNALLING and MEMBRANE TRANSPORT Mark Louie D. Lopez Department of Biology College of Science Polytechnic University of the Philippines

GENERIC SIGNALLING PATHWAY

CELL RESPONSE TO SIGNALS

IMPORTANT CHARACTERS IN PATHWAYS Messengers Kinase Ligand Receptors Signal Transduction Pathway

TRANSCRIPTION FACTORS Assist in initiating eukaryotic transcription Enhancers Promoter Gene DNA Transcription factors Activator proteins Other proteins RNA polymerase Bending of DNA Transcription

Nucleus Master control gene myod Other muscle-specific genes Embryonic precursor cell DNA OFF OFF

Nucleus Master control gene myod Other muscle-specific genes Embryonic precursor cell DNA OFF OFF 1 Myoblast (determined) Determination. Signals from other cells lead to activation of a master regulatory gene called myod, and the cell makes MyoD protein, a transcription factor. The cell, now called a myoblast, is irreversibly committed to becoming a skeletal muscle cell. mrna MyoD protein (transcription factor) OFF

Nucleus Master control gene myod Other muscle-specific genes DNA Embryonic precursor cell OFF OFF 1 Myoblast (determined) Determination. Signals from other cells lead to activation of a master regulatory gene called myod, and the cell makes MyoD protein, a transcription factor. The cell, now called a myoblast, is irreversibly committed to becoming a skeletal muscle cell. mrna MyoD protein (transcription factor) OFF 2 Differentiation. MyoD protein stimulates the myod gene further, and activates genes encoding other muscle-specific transcription factors, which in turn activate genes for muscle proteins. MyoD also turns on genes that block the cell cycle, thus stopping cell division. The nondividing myoblasts fuse to become mature multinucleate muscle cells, also called muscle fibers. mrna mrna mrna mrna Muscle cell (fully differentiated) MyoD Another transcription factor Myosin, other muscle proteins, and cell-cycle blocking proteins

PATTERNS OF CELL COMMUNICATION Autocrine Paracrine Encdocrine Neuroendocrine

AUTOCRINE

PARACRINE

ENDOCRINE

NEUROENDOCRINE

NEED TO TRANSPORT Cells maintain high K+ and low Na+ ICF K+ - rich ECF Na+, Cl- - rich Plasma & interstitial similar solute composition but no plasma proteins from the interstitium

GRADIENT Difference in concentration of substance on one to to another Chemical Gradient Electrical Gradient

Electric Potential Electrochemical gradient Chemical Concentration

GRADIENT

GIBB-DONNAN S EQUILIBRUIM refers to the uneven distribution of charged particles on one side of a semipermeable membrane. these particles are not able to evenly distribute themselves by diffusion across both sides of the membrane.

DONNAN S EQUILIBRUIM

MEMBRANE ELECTRIC POTENTIAL Electrochemical equilibrium The state at which the concentration gradient of an ion across a membrane is precisely balanced by the electric potential across the membrane. Electrochemical potential The electrical potential developed across a membrane due to a chemical concentration gradient of an ion that can diffuse across the membrane.

NERNST EQUATION The Nernst equation gives a formula that relates the numerical values of the concentration gradient to the electric gradient that balances it.

NERNST EQUATION R= gas constant/ gas constant, which is 8.31 (voltcoulomb)/(mol-k) T= absolute temperature F= faraday s constant/ 96500 coulombs/mol

NERNST EQUATION EXAMPLE

TYPES OF TRANSPORTATION Passive Transport allow water soluble substances (small polar molecules and ions) to pass through the membrane without any energy cost Active Transport The cell expends energy to transport water soluble substances against their concentration gradient

PASSIVE TRANSPORT Solute moves down its electrochemical gradient

PASSIVE TRANSPORT Requirements Membrane should be permeable Driving force electrochemical gradient or electrochemical potential energy difference Concentration gradient of solute Chemical potential energy difference Difference in voltage

PASSIVE TRANSPORT Fick s Law of Diffusion describes diffusion and can be used to solve for the diffusion coefficient

FICK S LAW

OSMOSIS Process of net movement of water caused by a concentration difference From a higher to a lower water concentration

OSMOTIC PRESSURE

OSMOLALITY Osmolality Concentration of a solution in terms of the number of particles

OSMOLALITY COMPUTATION

TONICITY

TONICITY Hemolysis Crenation

PASSIVE TRANSPORT Substances cross membrane thru Intrinsic membrane proteins Pores Channels Carriers

PORES Always open Non-gated channel Can allow molecules <45kDa Examples Porins Perforin NPC Aquaporin

PORES Dalton is the unit for atomic mass

PORES

CHANNELS Alternately open and close With movable barrier or gate Gated pore Undergo conformational transition between open and closed states

CHANNELS

CARRIERS Facilitated passive diffusion of small solutes (eg. Glucose) Mediate only downhill or passive transport Do not hydrolyze ATP or couple to ETC Each carrier protein has specific affinity for binding solutes Fixed number of carriers to transport X

CARRIERS

PASSIVE TRASPORT

ACTIVE TRANSPORT Process that can transfer a solute uphill across a membrane, against its electrochemical gradient Primary active transport (Direct) Secondary active transport (Indirect)

ACTIVE TRASPORT

PRIMARY ACTIVE TRASPORT Direct active transport Driving force needed for the net transfer of solute comes from the energy change associated with ATP hydrolysis Example: Na-K pump

Na-K PUMP In plasma membrane Each cycle: extrusion of 3Na+ and uptake of 2K+ with 1 ATP

Na-K PUMP

SECONDARY ACTIVE TRANSPORT Indirect active transport Co-transporter or Symport Exchanger or Antiport Driving force is provided by coupling the uphill movement of one solute to the downhill movement of another solute for which a favorable electrochemical gradient exists

CO-TRANSPORTER Symports Generally driven by energy of inward directed Na gradient Driven solute moves in the same direction as the driving solute

CO-TRANSPORTER

EXCHANGER Antiporters Driven solute moves in opposite direction of the driving solute Exchange cations for cations, anions for anions

BULK FLOW

ENDOCYTOSIS Process of ingestion of substances by the cell membrane Requires energy supplied by ATP Requires Ca++ Lysosomes Hydrolases Digestive vesicle

PINOCYTOSIS Ingestion of small globules of extracellular fluid Occurs continuously Pinocytic vesicle 100-200 nm The only means by which most large macromolecules esp proteins can enter cell

PINOCYTOSIS

PHAGOCYTOSIS Ingestion of large particles (bacteria, cells, degenerating tissue) Only certain cells have this capability Tissue macrophages Some WBC s Initiated when a particle binds with the receptors on the surface of the phagocyte

PHAGOCYTOSIS

EXOCYTOSIS Process of excretion of undigestible substances by the cell membrane Opposite of endocytosis Example Release of neurotransmitters from the presynaptic nerve endings Release of pancreatic enzyme from acinar cells of pancreas

EXOCYTOSIS

2 nd review Review Present a summary of the original article regarding the fluid-mosaic model of cell membrane Limit your presentation to 10 slides. The slide must include important aspect of the paper