EGR2 and SOX10 bind the PRX gene

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R-HSA-9619657
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Homo sapiens
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Periaxin (PRX) is a scaffolding protein that is part of a dystrophin:dystroglycan complex required for maintenance of the myelin sheath in Schwann cells. PRX homodimers interact with DRP2 to form a complex with dystroglycan at the basal lamina, anchoring the complex in the plasma membrane (Sherman et al, 2001; Han and Kursala, 2014). Mutations in PRX are associated with severe demyelinating peripheral neuropathies (Boerkoel et al, 2001; Guilbot et al, 2001).
Expression of PRX initiates earlier than EGR2 during peripheral nerve cell myelination, indicating an EGR2-independent mechanism early during myelination (Parkinson et al, 2003). Candidate regulators of this early expression include SOX10 and EGR1, which is expressed in embryonic Schwann cells and with EGR2 at postnatal day 1 (Topilko et al, 1997). Sustained, upregulated expression of PRX during myelination depends on the binding of EGR2 and SOX10 to a binding site within the first intron, 4.5 kb from the transcription start site (Jones et al, 2007; Srinivasan et al, 2012). Consistent with this, expression of PRX is decreased in EGR2 null mice (Nagarajan et al, 2001; Boerkoel et al, 2001).

Literature References
PubMed ID Title Journal Year
12799134 Regulation of the myelin gene periaxin provides evidence for Krox-20-independent myelin-related signalling in Schwann cells

Sharghi-Namini, S, Duran Alonso, MB, Dickinson, S, Brophy, PJ, Mirsky, R, Kinsella, MT, Jessen, KR, Bhaskaran, A, Sherman, DL, Parkinson, DB

Mol. Cell. Neurosci. 2003
11133365 Periaxin mutations cause recessive Dejerine-Sottas neuropathy

Stankiewicz, P, Lupski, JR, Leber, SM, Takashima, H, Rhee-Morris, L, Garcia, CA, Boerkoel, CF

Am. J. Hum. Genet. 2001
11430802 Specific disruption of a schwann cell dystrophin-related protein complex in a demyelinating neuropathy

Gillespie, CS, Fabrizi, C, Brophy, PJ, Sherman, DL

Neuron 2001
7935840 Krox-20 controls myelination in the peripheral nervous system

Babinet, C, Chennoufi, AB, Levi, G, Seitanidou, T, Schneider-Maunoury, S, Charnay, P, Topilko, P, Baron-Van Evercooren, A

Nature 1994
22492709 Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve

Jones, EA, Keles, S, Sun, G, Moran, JJ, Svaren, J, Jang, SW, Srinivasan, R, Krueger, C

Nucleic Acids Res. 2012
18634568 Interactions of Sox10 and Egr2 in myelin gene regulation

Nagarajan, R, Jones, EA, Mager, GM, Ward, RM, Chang, LW, Svaren, J, Jang, SW, Srinivasan, R, Gokey, NG

Neuron Glia Biol. 2007
11157804 A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease

LeGuern, E, Williams, A, Bareil, C, Verny, C, Delague, V, Claustres, M, Brophy, PJ, Ravisé, N, Megarbane, A, Brice, A, Sherman, DL, Guilbot, A

Hum. Mol. Genet. 2001
24675079 Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping

Kursula, P, Han, H

J. Biol. Chem. 2014
11394999 EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression

Milbrandt, J, Watson, M, Le, N, Svaren, J, Nagarajan, R, Araki, T

Neuron 2001
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