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    DCC Gene

    View times: 13
    Submitted by: Vivi Li
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    DCC Netrin 1 Receptor: The DCC gene provides instructions for making a protein called the netrin-1 receptor, which is involved in the development of the nervous system. 

    1. Normal Function

    This receptor has three major parts: an extracellular region that sticks out from the surface of the cell, a transmembrane region that anchors the receptor to the cell membrane, and an intracellular region that transmits signals to the interior of the cell. The extracellular region attaches (binds) to a substance (its ligand) called netrin-1, fitting together like a lock and its key. The binding of netrin-1 triggers signaling via the intracellular region of the receptor that helps direct the growth of specialized nerve cell extensions called axons. Axons transmit nerve impulses that signal muscle movement. Normally, movement signals from each half of the brain control muscles on the opposite side of the body. Binding of netrin-1 to its receptor inhibits axons from developing in ways that would carry movement signals from each half of the brain to the same side of the body.

    The netrin-1 receptor is also thought to act as a dependence receptor, which means it has different functions in the presence or absence of its ligand. In the case of the netrin-1 receptor, binding to its ligand triggers signaling related to nervous system development, as described above. When not bound to netrin-1, the netrin-1 receptor acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. Studies suggest that when the netrin-1 receptor is not bound to netrin-1, it triggers cell death (apoptosis).

    2. Health Conditions Related to Genetic Changes

    2.1 Congenital Mirror Movement Disorder

    At least 11 DCC gene mutations have been identified in people with congenital mirror movement disorder, a condition in which intentional movements of one side of the body are mirrored by involuntary movements of the other side. These mutations change single protein building blocks (amino acids) in the netrin-1 receptor or introduce a premature stop signal in the instructions for making the protein, resulting in an impaired or missing protein. Insufficient functional netrin-1 receptor protein impairs control of axon growth during nervous system development. As a result, movement signals from each half of the brain are abnormally transmitted to both sides of the body, leading to mirror movements.

    2.2 Cancers

    Deletions of genetic material that include the DCC gene have been found in more than 70 percent of colorectal cancers, as well as other cancerous tumors. This deletion is not inherited and is found only in the tumor cells. Deletion of the DCC gene results in the absence of the netrin-1 receptor. As a result, the netrin-1 receptor is not available to trigger apoptosis, resulting in the uncontrolled cell growth and division that leads to cancer.

    3. Other Names for This Gene

    • colorectal cancer suppressor

    • colorectal tumor suppressor

    • CRC18

    • CRCR1

    • DCC_HUMAN

    • deleted in colorectal cancer protein

    • deleted in colorectal carcinoma

    • IGDCC1

    • immunoglobulin superfamily DCC subclass member 1

    • immunoglobulin superfamily, DCC subclass, member 1

    • MRMV1

    • netrin receptor DCC

    • NTN1R1

    • tumor suppressor protein DCC

    This entry is adapted from https://medlineplus.gov/genetics/gene/dcc

    References

    1. Arakawa H. Netrin-1 and its receptors in tumorigenesis. Nat Rev Cancer. 2004Dec;4(12):978-87. Review.
    2. Depienne C, Cincotta M, Billot S, Bouteiller D, Groppa S, Brochard V, Flamand C, Hubsch C, Meunier S, Giovannelli F, Klebe S, Corvol JC, Vidailhet M, Brice A, Roze E. A novel DCC mutation and genetic heterogeneity in congenital mirrormovements. Neurology. 2011 Jan 18;76(3):260-4. doi: 10.1212/WNL.0b013e318207b1e0.
    3. Franz EA, Chiaroni-Clarke R, Woodrow S, Glendining KA, Jasoni CL, RobertsonSP, Gardner RJM, Markie D. Congenital mirror movements: phenotypes associatedwith DCC and RAD51 mutations. J Neurol Sci. 2015 Apr 15;351(1-2):140-145. doi:10.1016/j.jns.2015.03.006.
    4. Galléa C, Popa T, Billot S, Méneret A, Depienne C, Roze E. Congenital mirrormovements: a clue to understanding bimanual motor control. J Neurol. 2011Nov;258(11):1911-9. doi: 10.1007/s00415-011-6107-9.
    5. Mehlen P, Llambi F. Role of netrin-1 and netrin-1 dependence receptors incolorectal cancers. Br J Cancer. 2005 Jul 11;93(1):1-6. Review.
    6. Méneret A, Depienne C, Riant F, Trouillard O, Bouteiller D, Cincotta M, BitounP, Wickert J, Lagroua I, Westenberger A, Borgheresi A, Doummar D, Romano M, RossiS, Defebvre L, De Meirleir L, Espay AJ, Fiori S, Klebe S, Quélin C,Rudnik-Schöneborn S, Plessis G, Dale RC, Sklower Brooks S, Dziezyc K, Pollak P,Golmard JL, Vidailhet M, Brice A, Roze E. Congenital mirror movements: mutationalanalysis of RAD51 and DCC in 26 cases. Neurology. 2014 Jun 3;82(22):1999-2002.doi: 10.1212/WNL.0000000000000477.
    7. Méneret A, Trouillard O, Dunoyer M, Depienne C, Roze E. Congenital MirrorMovements. 2015 Mar 12 [updated 2020 Sep 24]. In: Adam MP, Ardinger HH, Pagon RA,Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet].Seattle (WA): University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK279760/
    8. Peng J, Charron F. Lateralization of motor control in the human nervoussystem: genetics of mirror movements. Curr Opin Neurobiol. 2013 Feb;23(1):109-18.doi: 10.1016/j.conb.2012.08.007.
    9. Srour M, Rivière JB, Pham JM, Dubé MP, Girard S, Morin S, Dion PA, Asselin G, Rochefort D, Hince P, Diab S, Sharafaddinzadeh N, Chouinard S, Théoret H, CharronF, Rouleau GA. Mutations in DCC cause congenital mirror movements. Science. 2010 Apr 30;328(5978):592. doi: 10.1126/science.1186463.
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