Cells: the basis for Life

Nearly all living things are made out of cells. The only exception is viruses and they still require host cells to survive. Cells are full of elaborate machinery and systems that work together to maintain life functions.

Many of the most successful life forms on earth are single-celled microbes. Through the evolution of multi-cellular eukaryotes, the beautiful intricacies and complexity found in a single cell organism have been retained. Although multi-cellular animals and plants may have lost the ability to survive as single cells, they have in turn gained incredible mechanisms for cell-cell communication as well as cell specialisation into tissues [1].

 



The inner city of the cell

We can liken a cell to a living city. The cell has city boundaries - the plasma membrane and this boundary acts as a defence keeping out unwanted molecules. Molecules can enter the cell through special proteins that act as the 'city gates'. These are discussed in more detail in 'surface structures'.

 

The library - the nucleus

Within the cell city there needs to be rules, laws, blueprints and instructions. These are held in the library of the cell - the nucleus. Of course, we're talking about cells so instead of books, we have DNA. The genetic information encoded in the DNA provides the instructions of how a cell needs to behave and make its various cellular structures. [2]

 

The atmosphere - the cytosol

The cell is filled with cytosol, a soluble substance full of protein, ions and other organic molecules. The cytosol is a bit like the cell's atmosphere. In the same way that the atmosphere we breathe has a particular make-up of constituents like nitrogen, oxygen and carbon dioxide, the cytosol maintains a balance of osmolarity and salts concentrations.  The cytosol is where protein synthesis and much of the cells metabolism takes place. [3]

 

The factories - ribosomes

DNA would not fare well in the cytoplasm; positively-charged cations would be attracted to the negatively charged DNA and enzymes would degrade it. As DNA damage is disastrous for a cell (it will lead to cell death or cancer), the DNA is enclosed within the nucleus. However, in order for a protein to be synthesised, the DNA 'message' must reach the ribosomes - the cell's 'protein factories'. Therefore DNA is transcribed into a complementary messenger (m)RNA strand. As mRNA has a rapid turnover rate damage is not such a problem.

 

The mRNA travels to ribosomes where the message is translated into an amino acid sequence using transfer (t)RNA and a protein is synthesised. As proteins are the fundamental building blocks of cells, we can think of the ribosomes as factories, manufacturing the protein ready to be used all over the cell [4,5].

 

Some proteins are synthesised by the ribosomes into the cytosol and are either sent to the ER after translation or straight to their final destination in the cell. Other proteins are translocated into the endoplasmic reticulum (ER) during translation. When this happens the ribosomes attach to the ER membrane, which gives it a rough appearance when visualised using electron microscopy [6].

 

Ribosomes are made from protein and ribosomal RNA. The ribosomal RNA is made in the nucleolus, which is a non-membrane bound region of the nucleus [7].

 

 

The Endoplasmic Reticulum (Green) and the nucleus (Blue)

The quality control centre - the endoplasmic reticulum (ER)

The ER acts like a quality control centre for the proteins made by the ribosomes. It has several mechanisms to ensure proteins are folded properly. If the protein cannot be folded correctly it is destroyed.

 

The ER can modify newly synthesised proteins via N-linked glycosylation. This process involves the linking of a large sugar-rich glycan to an asparagine (N) residue in the protein. N-linked glycosylation is important during the folding of some proteins [8].  

 

The ER also acts as a store for calcium ions used during cell signalling [9]. 

 

The sorting office - the Golgi apparatus

The Golgi apparatus acts as a sorting centre in the cell, packaging up proteins and lipids into vesicles ready to be sent off to their cellular destinations. This includes proteins found in other organelles as well as proteins that leave the cell and are secreted.

 

The Golgi apparatus is made of stacks and vesicles that are arranged in ribbon-like structures, usually near the nucleus. The stacks are classified into three types; the cis-Golgi nearest the nucleus, the trans-Golgi furthest from the nucleus and medial-Golgi which are situated between the cis and trans. Each type of stack has a distinct subset of proteins [10].

 

The Golgi apparatus (green) and nuclei (blue)

Certain protein modifications take place in the Golgi, such as O-linked glycosylation, which involves the addition of glycans to either serine or threonines via their OH groups. This modification usually occurs extensively on secretory proteins like mucins that are needed for mucus production. 

 

Another modification that takes place in the Golgi is the trimming of N-linked glycans that were added to a protein in the ER. Modification of these glycans can determine where the resulting protein is sent [11].

 

 

 

The delivery trucks - vesicles

Proteins and lipids that have been made inside the cell or absorbed by the cell need to be taken to their correct destination. This is where vesicular structures come in. There are several types of vesicles, but they all share some common features. They are small, usually spherical, membranous structures with a hydrophilic centre.

Lysosomes (Red) and DAPI (Blue)

ER-Golgi Iintermediate compartments (ERGIC) are vesicular structures that shuttle between the ER and Golgi. The ER is directly upstream of the Golgi in the secretory pathway, however, physically the ER can be located far away and from the Golgi inside the cell. The ER network stretches from the nuclear envelope right the way to cell periphery. As the Golgi is usually in a perinuclear position, retrograde transport via the ERGIC is needed to shuttle proteins from the ER to Golgi for sorting [12].

 

Secretory vesicles transport proteins and lipids in the secretory pathway from the Golgi apparatus to the cell surface. This can either include components on the plasma membrane such as receptors and membrane proteins or proteins that need to be secreted out of the cell like hormones and extra cellular matrix components. 

 

Endosomes are vesicles that are involved in taking up - or endocytosing - proteins, lipids and carbohydrates from outside the cell. The endocytic pathway is complex and as such the endosomes can be divided into distinct groups according to where they are found in this pathway. The early endosomes contain membranes that have recently been endocytosed. They can either mature into late endosomes or become recycling endosomes that send their contents back to the plasma membrane. The late endosomes often merge to form much larger mulit-vesicular bodies. Late endosomes can either deliver their cargoes to the Golgi for sorting and re-delivery or send the proteins to the lysosomes for degradation. Different endosomes can be distinguished by the proteins they contains and those that regulate them. An example of this is the Rab GTPase proteins that regulate membrane trafficking - different endosome compartments are regulated by different Rab proteins [13].

 

Lysosomes are where non-cytoplasmic proteins are degraded so can be thought of as the rubbish dump of the cell. They are highly acidic (pH4.5). If a vesicle contains cargo that needs to be degraded it will take it to the lysosome where the cargo is destroyed  [14].

 

Mitochondria

The power plant - the mitochondria

The mitochondria produce ATP, which is considered the energy 'currency' of the cell. We can think of the mitochondria as a power station and the ATP it produces is like the cell’s electricity - transporting and quickly releasing energy needed for cellular functions. 

 

The mitochondria have an inner and an outer membrane that encase the intermembrane space. The centre of the mitochondria is called the matrix.

The inner membrane contains the membrane proteins involved in the electron transport chain, which produces hydrogen ions that are stored in the intermembrane space. The inner membrane also contains an enzyme called ATP-synthase that pumps these hydrogen ions into the matrix and simultaneously phosphorylates ADP, producing ATP. The inner membrane forms long protrusions into the matrix, called cristae, to maximise the area where this ATP production can take place [15].

 

The mitochondria carry non-nuclear DNA which is derived maternally. They can transcribe this DNA and translate it to protein using their own ribosomes. These ribosomes differ from the cytoplasmic ribosomes and are structurally similar to prokaryotic ribosomes. This, in combination with their double membrane composition and size has lead to the theory that that early in their evolution, eukaryotic cells engulfed prokaryotic cells that eventually became the mitochondria we have today [16].

 

 

The transport network - the cytoskeleton

Every city needs transport infrastructure and in the cell this is where the cytoskeleton comes in. There are three main types of filaments in the cytoskeleton - intermediate filaments, microtubules and actin filaments.

 

There are several types of intermediate filaments, including keratin, vimentin and lamin. Their main role is to  provide stuctural support and tensile strength.

 

Microtubules (Red) Two cells in cytokensis

Microtubules are polarised filaments that form in a GTP dependent manner from tubulin dimers. Microtubules are anchored at the microtubule organising centre that is usually situated centrally in the cell near the nucleus. The microtubules emanate out towards the edge of the cell and are in a constant flux between growing and shrinking. During mitosis, microtubules reorganise to form spindles that pull the chromosomes apart into the newly forming daughter cells. Microtubule-associated motor proteins can 'walk' along microtubules and carry various cellular cargos around the cell - a bit like freight trains.

 

The final type of cytoskeleton structure is actin. Filamentous actin is polymerised in an ATP-dependent manner from actin monomers. Actin plays a role in organelle transport, membrane budding, cell migration and cytokenesis. Just like microtubules, actin has specific motor proteins that can walk along the filaments [17]. 

 

 

Running the city

In order for a cell to survive, all of its components need to work together. Although the organelles discussed here are separate entities, the pathways they are involved with overlap and intersect. In a city there would be no point having a library if no one could read or having a sorting office with no delivery trucks. Equally, in the cell you need ribosomes to covert the DNAs genetic information into protein and without vesicles to deliver cargo, what would be the point of the Golgi apparatus sorting it? The organelles work together to keep the cell alive and working as a whole. This is mirrored when cells work together in tissues - if we think of a cell as a city, then the tissue is the country and the body is the world. As such, the body relies on its individual cells and all their internal structures to work together and allow the whole organism to thrive. 

 

References

1. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p3-45.

2. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p229-374

3. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p660

4.  Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p10

5.  Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p299-373

6. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p689-690

7. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p331-332

8. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p689-709

9. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p861-862

10. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p736-737

11. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p727-745

12. Judith Klumperman, Transport between ER and Golgi, Current Opinion in Cell Biology, Volume 12, Issue 4, 1 August 2000, Pages 445-449

13. Mary W. McCaffrey, Andrew J. LindsayEncyclopedia of Biological Chemistry, 2004, Pages 629-634

14. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p739-740

15. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p769-781

16. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science. p808-821

17. Alberts, B; Johnson, A; Lewis J; Raff, M; Roberts K; Walter, P (2002).Molecular Biology of The Cell. 4th ed. New York: Garland Science p908-981

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