Melanocytes, Melanosomes, and Keratinocytes

7

MELANOCYTES and MELANOSOMES

Textbook: pp 453-456 (kinesin and dynein; p 461 myosins)

Melanocytes ( melas = black or dark) are the cells in our bodies that produce melanosomes, which are membrane-bound organelles producing the dark pigment called melanin. The melanocytes pass the the melanosomes on to other cells, for example keratinocytes in the epidermis and developing hair cells. Melanin is made from the amino acid tyrosine and the first enzyme in its biosynthesis is called tyrosinase. Melanin is an insoluble polymer, and much of the polymerization does not require enzymes.

You do not need to know these formulars. But you should know:

(1)  The enzyme tyrosinase catalyses two separate oxidation reactions.

(2)  The second oxidation is the oxidation of a quinol to a quinonone.

(3)  Hydrogen peroxide (H2O2) will be produced as a result of this reaction! Melasomes do contain catalase, but but much of the H2O2 produced is actually used to non-enymatically oxidase later products in the melanin biosynthesis pathway.

The biological functions of melanin include:

(1)  Serve as a natural sunscreen

(2)  Protect eyes from photodamage

(3)  Camouflage (e.g. in fish and shrimp)

(4)  Sign of sexual fitness (e.g. black markings in male birds)

The melanosomes are derived from the Golgi bodies, although their biogenesis is complex and involves considerable involvement with other mebranous structures after the trans-Golgi network. We can draw the basic steps as follows:

Melanosomes and camouflage

Consider a small in the Antigonish estuary that wishes to blend in with a whitish sand sediment or a dark mud sediment. To avoid being seen on a white background it wants to have its melansomes (in melanocytes) as inconspicous as possible. So it moves them all form a a sphere around the nucleus, so the melanocytes will just look like very small dots. But to blend into the dark background, it wants its melanosomes distributed throughout the cytoplasm of the melanocyte, so its skin looks dark.

To have this change in melanosome distribution within the cell, the melanosomes must move! They move on mictrotubules when moving outwards from the center of the cell (i.e. from around the nucleus) and on actin microfilamnts for more “small scale” movements. They need “walker molecules” to move them around:

The “walker molecules” for movement on the microtubules are kinesin (away from the nucleus) and dynein (back towards the nucleus). The “walker molecules” for the movement on the actin microfilaments are myosins.

All three of these “walker molecules” have ATPase active sites. Thus the energy for the movement of the “walker molecules” comes from ATP hydrolysis.

The three types of “walker molecules” (kinesin, dynein, and myosins) all have a somewhat similar structure that I will draw as shown below:

All three types of “walker molecules” are bound to the moving melanosome! Hence, they can at anytime move in either direction on microtubules, and they can transfer rapidly to movement on actin microfilaments. Myosins can move in both directions on actin microfilamnets.

The numerous causes of albinism

Listed below are the possible causes of albinism (the lack of functional melanosomes). Thinking about these causes serves to review all the thigns that go on in the RER/Golgi system:

(1)  Mutation in the tyrosinase gene that prevents the formation of an enzyme with little or no tyrosinase activity. (No melanin formation)

(2)  Mutation in the signal sequence for tyrosinase. (Tyrosinase may be fully functional, but it is not inserted into the RER lumen and so none will appear in the melanosomes)

(3)  Mutation that does not affect the signal sequence or the tyrosinase to a serious extent, but does cause improper folding in the RER lumen. (The mis-folded tyrosinase is not packaged into transport vesicles, and so it never reaches the Golgi bodies.)

(4)  Mutation in the tyrosine transport system gene. (The melanosomes cannot transport in the tyrosine they require for the synthesis of melanin).

Can you think of any other mutations that would cause melanism? Considering the above,why is albinism usually a recessive genetic trait rather than a dominant genetic trait?

Melanosomes as a sunscreen

The melanosomes are are full of melanin which is a natural sunscreen. It absorbs ultraviolet light (UV) and thus protects DNA from UV damage which causes mutations. The following points can be made about the role of melanosomes:

(1)  Only the cells called melanocytes make melansomes.

(2)  Melanosomes are derived from Golgi bodies.

(3)  Melanosomes are transferred to the keratinocytes that are in a layer above the basal cell layer. Most of the cells in the basal layer are there to divide are produce the overlying skin cells. The melaocytes are also in the basal cell layer.

(4)  The keratinocytes engulf the tips of the long process of the melanocytes. The engulfed melanocyte “tips” contain melansomes which have migrated there from the center ot he melanocytes (i.e. from around the nucleus where the Golgi bodies are located.

How do the melanosomes move to the tips of the long processes of the melanocytes?

The following points can be made:

(1)  The “long distance” movement of melansomes in the melanocytes is on microtubules.

(2)  Shorter distance movement is on actin microfilaments.

(3)  The “walker molecules” for the movement of melanosomes on the microtubules are kinesin and dynein. They move in different directions on the microtubules.

(4)  The “walker molecules” for movement on the actin microfilaments are the myosins.

(5)  The energy for the “walker molecules” is ATP hydrolysis.

(6)  All three “walker molecules” are attached to a melanosomes at one time. This means the melanosomes can walk both ways on the microtubules and can also “hop over” to an actin microfilaments when necessary. The cell cytoplasm is a very dense place, and the migrating melanosomes will “run into” many obstructions on the forward movement on the microtubules. Thus being able to “back-up” on a microtubule or to temporarily “hop over” to an actin microfilament to get out of the way of the obstruction.

SHORT ANSWER = DIAGRAMS + PARAGRAPH(S)

6 OUT 0F 8 6 x 14 = 84

ESSAY (SOME DIAGRAMS) = 16 MARKS