User:Kelseyfish1189/Peripherin Proposal

Wikipedia Proposal: Peripherin

Presented by: Kelsey Fisher and Kevin Melnick.

Main points

General description:

Peripherin, also known as PRPH, is a gene located on chromosome 12 that codes for the protein peripherin. Peripherin is a type III intermediate filament found in neurons of the peripheral nervous system. It is produced in both the peripheral nervous system and in some islet cells.

Function

• Several peripherin protein molecules polymerize to form intermediate filaments
• Able to heteropolymerize with other type III intermediate filaments or neurofilament proteins
• Exact function not yet solidified, as knockout mice show no significant change in development or lifespan. This may indicate that the PRPH gene may have a redundant role.

Gene Information

• Location on chromosome 12
• Post translational modification
• Alternative splicing patterns

Clinical History

• Knockout studies in mice are helping to pinpoint the exact functions of PRPH. While peripherin was originally thought to play a vital role in locomotor activities and energy expenditure, mice that have a deleterious peripherin gene develop normally and do not show signs of any handicap. However, the loss of a small amount of unmyelinated sensory fibers has been observed in such mice. This is indicative of periphein's role in axonal growth and repair.

Role in Disease

• Several mutations in PRPH can lead to an increased risk of Amyotrophic lateral sclerosis (also known as Lou Gehrig's disease) due to aggregation of this protein. This occurs when peripherin is overexpressed in the cell and aggregates in the somata and axons.

• Peripherin has also been identified as a self antigen in murine models of insulin-dependent diabetes mellitus.

Division of Workload

• We have decided to try to do as much of this project together as possible to ensure that changes to the page can be approved by all members of the group.

References

1. Eriksson, K., Zhang, S., Lin, L., Larivière, R., Mignot, E. & Julien, J. (2008). The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse. BMC Neuroscience, 9(26), DOI: doi:10.1186/1471-2202-9-26
2. John Foley, Catherine A. Ley, Linda M. Parysek, The Structure of the Human Peripherin Gene (PRPH) and Identification of Potential Regulatory Elements, Genomics, Volume 22, Issue 2, 15 July 1994, Pages 456-461, ISSN 0888-7543, 10.1006/geno.1994.1410. (http://www.sciencedirect.com/science/article/pii/S0888754384714108)
3. Fuchs, E., & Weber, K. (1994). Intermediate filaments: structure, dynamics, function, and disease. Annual Review, 63, 345-382.
4. Meins M, Grüning G, Blankenagel A, Krastel H, Reck B, Fuchs S, Schwinger E, Gal A. Heterozygous 'null allele' mutation in the human peripherin/RDS gene. Hum Mol Genet. 1993 Dec;2(12):2181-2. PMID 8111389.
5. Vale, Ronald. Guidebook to the Cytoskeletal and Motor Proteins. Ed. Thomas Kreis. 2nd ed. New York: Sambrook & Tooze Partnership, 1999. Print.