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Posts Tagged ‘centromere’


Introduction to Subcellular Structure

Author and Curator: Larry H. Bernstein, MD, FCAP  

 

 

The following chapter of the metabolism/transcriptomics/proteomics/metabolomics series deals with the subcellular structure of the cell.  This would have to include the cytoskeleton, which has a key role in substrate and ion efflux and influx, and in cell movement mediated by tubulins.  It has been extensively covered already.  Much of the contributions here are concerned with the mitochondrion, which is also covered in metabolic pathways.  The ribosome is the organelle that we have discussed with respect to the transcription and translation of the genetic code through mRNA and tRNA, and the therapeutic implications of SiRNA as well as the chromatin regulation of lncRNA.

We have also encountered the mitochondrion and the lysosome in the discussion of apoptosis and autophagy, maintaining the balance between cell regeneration and cell death.

I here list the organelles:

  1. Nucleus
  2. Centrosome
  3. Nuclear Membrane
  4. Ribososome
  5. Endoplasmic Reticulum
  6. Mitochondria
  7. Lysosome
  8. Cytoskeleton
  9. Golgi apparatus
  10. Cytoplasm
cell_organelle_quiz

cell_organelle_quiz

http://www.youtube.com/watch?feature=player_embedded&v=JufLDxmCwB0

http://www.youtube.com/watch?feature=player_embedded&v=FFrKN7hJm64

Golgi Apparatus

Found within the cytoplasm of both plant and animal cells, the Golgi is composed of stacks of membrane-bound structures known as cisternae (singular: cisterna). An individual stack is sometimes called a dictyosome (from Greek dictyon: net + soma: body), especially in plant cells. A mammalian cell typically contains 40 to 100 stacks. Between four and eight cisternae are usually present in a stack; however, in some protists as many as sixty have been observed. Each cisterna comprises a flat, membrane-enclosed disc that includes special Golgi enzymes which modify or help to modify cargo proteins that travel through it.

The cisternae stack has four functional regions: the cis-Golgi network, medial-Golgi, endo-Golgi, and trans-Golgi network. Vesicles from the endoplasmic reticulum (via the vesicular-tubular clusters) fuse with the network and subsequently progress through the stack to the trans-Golgi network, where they are packaged and sent to their destination.

The Golgi apparatus is integral in modifying, sorting, and packaging these macromolecules for cell secretion (exocytosis) or use within the cell. It primarily modifies proteins delivered from the rough endoplasmic reticulum, but is also involved in the transport of lipids around the cell, and the creation of lysosomes.  Enzymes within the cisternae are able to modify the proteins by addition of carbohydrates (glycosylation) and phosphates (phosphorylation). In order to do so, the Golgi imports substances such as nucleotide sugars from the cytosol. These modifications may also form a signal sequence which determines the final destination of the protein. For example, the Golgi apparatus adds a mannose-6-phosphate label to proteins destined for lysosomes.

The Golgi plays an important role in the synthesis of proteoglycans, which are molecules present in the extracellular matrix of animals. It is also a major site of carbohydrate synthesis. This includes the production of glycosaminoglycans (GAGs), long unbranched polysaccharides which the Golgi then attaches to a protein synthesised in the endoplasmic reticulum to form proteoglycans. Enzymes in the Golgi polymerize several of these GAGs via a xylose link onto the core protein. Another task of the Golgi involves the sulfation of certain molecules passing through its lumen via sulfotranferases that gain their sulfur molecule from a donor called PAPS. This process occurs on the GAGs of proteoglycans as well as on the core protein. Sulfation is generally performed in the trans-Golgi network. The level of sulfation is very important to the proteoglycans’ signalling abilities, as well as giving the proteoglycan its overall negative charge.

The phosphorylation of molecules requires that ATP is imported into the lumen of the Golgi and utilised by resident kinases such as casein kinase 1 and casein kinase 2. One molecule that is phosphorylated in the Golgi is apolipoprotein, which forms a molecule known as VLDL that is found in plasma. It is thought that the phosphorylation of these molecules labels them for secretion into the blood.

The Golgi has a putative role in apoptosis, with several Bcl-2 family members localised there, as well as to the mitochondria. A newly characterized protein, GAAP (Golgi anti-apoptotic protein), almost exclusively resides in the Golgi and protects cells from apoptosis by an as-yet undefined mechanism.

The vesicles that leave the rough endoplasmic reticulum are transported to the cis face of the Golgi apparatus, where they fuse with the Golgi membrane and empty their contents into the lumen. Once inside the lumen, the molecules are modified, then sorted for transport to their next destinations. The Golgi apparatus tends to be larger and more numerous in cells that synthesize and secrete large amounts of substances; for example, the plasma B cells and the antibody-secreting cells of the immune system have prominent Golgi complexes.

Those proteins destined for areas of the cell other than either the endoplasmic reticulum or Golgi apparatus are moved towards the trans face, to a complex network of membranes and associated vesicles known as the trans-Golgi network (TGN). This area of the Golgi is the point at which proteins are sorted and shipped to their intended destinations by their placement into one of at least three different types of vesicles, depending upon the molecular marker they carry.

Nucleus_ER_golgi

Nucleus_ER_golgi

Diagram of secretory process from endoplasmic reticulum (orange) to Golgi apparatus (pink). 1. Nuclear membrane; 2. Nuclear pore; 3. Rough endoplasmic reticulum (RER); 4. Smooth endoplasmic reticulum (SER); 5. Ribosome attached to RER; 6. Macromolecules; 7. Transport vesicles; 8. Golgi apparatus; 9. Cis face of Golgi apparatus; 10. Trans face of Golgi apparatus; 11. Cisternae of the Golgi Apparatus

Exocytotic vesicles

After packaging, the vesicles bud off and immediately move towards the plasma membrane, where they fuse and release the contents into the extracellular space in a process known as constitutive secretion. (Antibody release by activated plasma B cells)

Secretory vesicles

After packaging, the vesicles bud off and are stored in the cell until a signal is given for their release. When the appropriate signal is received they move towards the membrane and fuse to release their contents. This process is known as regulated secretion. (Neurotransmitter release from neurons)

Lysosomal vesicles

Vesicle contains proteins and ribosomes destined for the lysosome, an organelle of degradation containing many acid hydrolases, or to lysosome-like storage organelles. These proteins include both digestive enzymes and membrane proteins. The vesicle first fuses with the late endosome, and the contents are then transferred to the lysosome via unknown mechanisms.

http://en.wikipedia.org/wiki/Golgi_apparatus

Lysosome (derived from the Greek words lysis, meaning “to loosen”, and soma, “body”) is a membrane-bound cell organelle found in animal cells (they are absent in red blood cells). They are structurally and chemically spherical vesicles containing hydrolytic enzymes, which are capable of breaking down virtually all kinds of biomolecules, including proteins, nucleic acids, carbohydrates, lipids, and cellular debris.  Lysosomes are responsible for cellular homeostasis for their involvements in secretion, plasma membrane repair, cell signalling and energy metabolism, which are related to health and diseases. Depending on their functional activity their sizes can be very different, as the biggest ones can be more than 10 times bigger than the smallest ones. They were discovered and named by Belgian biologist Christian de Duve, who eventually received the Nobel Prize in Physiology or Medicine in 1974.

Enzymes of the lysosomes are synthesised in the rough endoplasmic reticulum. The enzymes are released from Golgi apparatus in small vesicles which ultimately fuse with acidic vesicles called endosomes, thus becoming full lysosomes. In the process the enzymes are specifically tagged with mannose 6-phosphate to differentiate them from other enzymes. Lysosomes are interlinked with three intracellular processes namely phagocytosis, endocytosis and autophagy. Extracellular materials such as microorganisms taken up by phagocytosis, macromolecules by endocytosis, and unwanted cell organelles are fused with lysosomes in which they are broken down to their basic molecules. Thus lysosomes are the recycling units of a cell.

http://en.wikipedia.org/wiki/Lysosome

The endoplasmic reticulum (ER) is a type of organelle in the cells of eukaryotic organisms that forms an interconnected network of flattened, membrane-enclosed sacs or tubes known as cisternae. The membranes of the ER are continuous with the outer membrane of the nuclear envelope. Endoplasmic reticulum occurs in most types of eukaryotic cells, including the most primitive Giardia, but is absent from red blood cells and spermatozoa. There are two types of endoplasmic reticulum, rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). The outer (cytosolic) face of the rough endoplasmic reticulum is studded with ribosomes that are the sites of protein synthesis. The rough endoplasmic reticulum is especially prominent in cells such as hepatocytes where active smooth endoplasmic reticulum lacks ribosomes and functions in lipid metabolism, carbohydrate metabolism, and detoxification and is especially abundant in mammalian liver and gonad cells. The lacey membranes of the endoplasmic reticulum were first seen in 1945 by Keith R. Porter, Albert Claude, Brody Meskers and Ernest F. Fullam, using electron microscopy.

http://en.wikipedia.org/wiki/Endoplasmic_reticulum

endoplasmic_reticulum

endoplasmic_reticulum

https://2cslacardano.wikispaces.com/file/view/Cell7.png/338811858/408×313/Cell7.png

Cytoskeleton

The Effects of Actomyosin Tension on Nuclear Pore Transport
Rachel Sammons
Undergraduate Honors Thesis
Spring 2011

The cytoskeleton maintains cellular structure and tension through a force balance with the nucleus, where actomyosin is anchored to the nuclear envelope by nesprin integral proteins. It is hypothesized that the presence or absence of this tension alters the transport of molecules through the nuclear pore complex. We tested the effects of cytoskeletal tension on nuclear transport in human umbilical vein endothelial cells (HUVECs) by performing fluorescence recovery after photo-bleaching (FRAP) experiments on the nuclei to monitor the passive transport of the molecules through nuclear pores.

Using myosin inhibitors, as well as siRNA transfections to reduce the expression of nesprin-1, we altered the nucleo-cytoskeletal force balance and monitored the effect of each on the nuclear pore. FRAP data was fit to a diffusion model by assuming pseudo-steady state inside the nuclear pore, perfect mixing within both the cytoplasm and the nucleus, and no intracellular binding of the fluorescent probes. From these results and a model from the current literature relating diffusion rate constants to nuclear pore radii, we were able to determine that changing cytoskeletal tension alters nuclear pore size and passive transport.

nuclear pores in nuclear envelope

nuclear pores in nuclear envelope

image of nuclear pores on the external surface of the nuclear envelope

nuclear envelope and FG filaments

nuclear envelope and FG filaments

nuclear envelope and FG filaments

Figure 1: The structure and location of the nuclear pore, shown by (a) AFM image of nuclear pores on the external surface of the nuclear envelope[5] and (b) computer model cross-section. The nuclear envelope is shown in cyan, and FG filaments in blue can be seen throughout the channel. The nuclear basket extends into the nucleoplasm.

Fusion-pore expansion during syncytium formation is restricted by an actin network

A Chen, E Leikina, K Melikov, B Podbilewicz, MM. Kozlov and LV. Chernomordik,*
J Cell Sci 1 Nov 2008;121: 3619-3628. http://dx.doi.org:/10.1242/​jcs.032169

Effects of actin-modifying agents indicate that the actin cortex slows down pore expansion. We propose that the growth of the strongly bent fusion-pore rim is restricted by a dynamic resistance of the actin network and driven by membrane-bending proteins that are involved in the generation of highly curved intracellular membrane compartments.

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