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Part 1a: Cell Functions

OK, now we're into the Brons lecture material. It is also cell bio but presented very differently than Zwickey's. I have his powerpoint presentations printed out, and will try to glean the "song" while not worrying too much about the words. Much of it seems extremely basic to me, and the rest is totally unfamiliar and unexplained. What do you think?

What do cells do? They proliferate, via mitosis (regular cell division) and meiosis (fancy division that yields gametes which join to make a zygote). They differentiate into specialized cells. They metabolize (break down some things and build other things). All of these functions are prompted by signaling factors (to divide and differentiate) and food and oxygen (for metabolism).

Later on he gives four cellular processes that are involved in embryo formation: 1) proliferation 2) specialization 3) interaction and 4) movement. These processes are induced by 1) transcription and regulatory factors 2) signaling molecules 3) receptor molecules and 4) signal transduction.

The products of a cell are used either internally or externally. Intracellular products are used for building cell structures, as enzymes for reactions in the cell, and signalling pathways. Secreted products are used in the extracellular matrix and as communications.

Is this general enough?

Differentiation is how a nonspecific cell develops a specialized function in response to a signal. Differentiation depends on the regulation of protein synthesis. The first cells (created by cleavage after fertilization) are totipotent, meaning they can become any kind of cell. After a while these split into ecto-, meso- and endo-derm, which are pluripotent cells. They are capable of producing a specific lineage from the germ cell layers seen in gastrulation.

Gastrulation = a phase early in the development of animal embryos, during which the morphology of the embryo is dramatically restructured by cell migration. Gastrulation varies in different phyla. Gastrulation is followed by organogenesis, when individual organs develop within the newly formed germ layers.

Committed cells are differentiated far enough that they must become part of a specific organ or tissue.

One Brons slide says "many cells remain determined in that they are committed to becoming a tissue type, but remain undifferentiated in a 'stem cell' state." What does he mean by determined??? A cell can be determined AND committed but not yet differentiated....I think that's what he means.

The regulation of protein synthesis is done 1) internally by transcription and gene regulatory factors and 2) externally by signaling factors and their receptors.

1) DNA is selectively transcribed to mRNA.
2) mRNA is selectively translated to polypeptide chains using tRNA and ribosomes
3) polypeptide chains get combined wtih oligosaccharides in the rough ER. n-linked glycosylation occurs.
4) polypeptide chains are folded or dismantled, depending on enzymes present
5) protein parts are transported to the golgi apparatus where they are further modified and assembled. n and o-linked glycosylation.
6) protiens are set up for secretion, insertion into a membrane, or retention in the cell.

transcription factors = TF = proteins that bind to particular genes along the DNA that are to be activated or repressed.

homeobox genes = The most conservative genes, meaning every organism has them. They encode homeodomain proteins, and important type of TF. Homeobox genes encode transcription factors which typically switch on cascades of other genes, for instance all the ones needed to make a leg. The homeodomain binds DNA in a specific manner.

a homeobox = a DNA sequence found within genes that are involved in the regulation of development (morphogenesis) of animals, fungi and plants. Genes that have a homeobox are called homeobox genes and form the homeobox gene family. A homeobox is about 180 base pairs long; it encodes a protein domain (the homeodomain) which can bind DNA.

homeodomain TF = a common form of homeodomain protein, helix turn helix. Usually binds to genes that initiate patterns of gene expression. The specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the promoter region of their target genes as complexes with other TFs, often also homeodomain proteins. Such complexes have a much higher target specificity than a single homeodomain protein.

hox genes = A subgroup of homeobox genes found in a special gene cluster, the Hox cluster (also called Hox complex). Hox genes function in patterning the body axis. Thus, by providing the identity of particular body regions, Hox genes determine where limbs and other body segments will grow in a developing fetus or larva. Mutations in any one of these genes can lead to the growth of extra, typically non-functional body parts in invertebrates, for example antennapedia complex in Drosophila, which results in a leg growing from the head in place of an antenna and is due to a defect in a single gene. Mutation in vertebrate Hox genes usually results in miscarriage.

regulatory factors = RF = helix-loop-helix proteins, lumped onto parts of the DNA, binds to regulator factors made by other genes, bind to specific regulatory genes, help position RNA polymerase, separate DNA strands to permit transcription, release RNA polymerase from promoter once transcription begins

promoter region = TATA, where transcription begins on a specific gene

DNA looping permits contact between regulatory proteins and interactions between genes, so those lumps of RF's that are scattered all up and down a strip of DNA can all work together like pieces of a puzzle to get the RNA polymerase started reading a gene. Final transciptional activity of a gene results from competition among activator and repressor regulatory genes, ie: biological equilibrium between opposing forces.

I'm so glad I looked all that up. The homeobox stuff was presented but not explained in lecture. Don't tell the prof, but wikipedia made all the difference in my comprehension!

1b: Cell Signaling

Signaling factors are protein-based molecules secreted by cells that communicate with other cells. Growth factors (GF) are one kind of SF. A few kinds of GFs include transforming GFs, Fibroblast GFs, Wnt -wingless types, Hedgehogs (sonic, desert, Indian, tiggy-winkle). These factors can stimulate expression of a gene, or inhibit gene expression, or probably both at the same time.

Receptor molecules are located in the cell membrane or the cytoplasm, and activate protein kinases via phosphorylation either directly or via second messengers. Notch type receptors can inhibit cell differentiation.

second messenger system = A method of cellular signalling where the signalling molecule does not enter the cell, but rather utilizes a cascade of events that transduces the signal into a cellular change. Secondary messengers are a component of signal transduction cascades. Secondary messenger systems utilize receptors on the surface of the plasma membrane which are generally coupled to a kinase on the interior surface of the membrane. The kinase then phosphorylates another molecule (frequently cAMP) which carries out another action. Secondary messengers are associated with many hormones, but they are NOT used by steroid hormone receptors or ligand-gated ion channels.

notch type receptor = One cell differentiates and stops the surrounding cells from doing the same thing. The Notch signaling mechanism is an example of juxtacrine signalling in which two adjacent cells must make physical contact in order to communicate. This requirement for direct contact allows for very precise control of cell differentiation during embryonic development. In the worm Caenorhabditis elegans, two cells of the developing gonad each have an equal chance of terminally differentiating or becoming a uterine precursor cell that continues to divide. The choice of which cell continues to divide is controlled by competition of cell surface signals. One cell will happen to produce more of a cell surface protein that activates the Notch receptor on the adjacent cell. This activates a feedback system that reduces Notch expression in the cell that will differentiate and increases Notch on the surface of the cell that continues as a stem cell.

juxtacrine = signaling in which adjacent cells touch

Many of the same mechanisms that produce the embro also help maintain and heal tissues throughout life. Factors that differentiate and maintain cells include 1) signaling factors (positional factors) 2) environmental influences on migration 3) hormones and growth factors 4) local factors such as autocrines, paracrines, and extracellular matrix.

autocrine = self signaling; a cell secretes a hormone, or chemical messenger (called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cell.

paracrine = diffused signal from nearby cell; the target cell is close to ("para" = alongside of or next to, but this strict prefix definition is not meticulously followed here) the signal releasing cell.



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