Reactome | PRX gene expression

PRX gene expression

Stable Identifier

R-HSA-9619667

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm, plasma membrane

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
11133365	Periaxin mutations cause recessive Dejerine-Sottas neuropathy Boerkoel, CF, Takashima, H, Stankiewicz, P, Garcia, CA, Leber, SM, Rhee-Morris, L, Lupski, JR	Am. J. Hum. Genet.	2001
12799134	Regulation of the myelin gene periaxin provides evidence for Krox-20-independent myelin-related signalling in Schwann cells Parkinson, DB, Dickinson, S, Bhaskaran, A, Kinsella, MT, Brophy, PJ, Sherman, DL, Sharghi-Namini, S, Duran Alonso, MB, Mirsky, R, Jessen, KR	Mol. Cell. Neurosci.	2003
11430802	Specific disruption of a schwann cell dystrophin-related protein complex in a demyelinating neuropathy Sherman, DL, Fabrizi, C, Gillespie, CS, Brophy, PJ	Neuron	2001
22492709	Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve Srinivasan, R, Sun, G, Keles, S, Jones, EA, Jang, SW, Krueger, C, Moran, JJ, Svaren, J	Nucleic Acids Res.	2012
9418958	Differential regulation of the zinc finger genes Krox-20 and Krox-24 (Egr-1) suggests antagonistic roles in Schwann cells Topilko, P, Levi, G, Merlo, G, Mantero, S, Desmarquet, C, Mancardi, G, Charnay, P	J. Neurosci. Res.	1997
18634568	Interactions of Sox10 and Egr2 in myelin gene regulation Jones, EA, Jang, SW, Mager, GM, Chang, LW, Srinivasan, R, Gokey, NG, Ward, RM, Nagarajan, R, Svaren, J	Neuron Glia Biol.	2007
11157804	A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease Guilbot, A, Williams, A, Ravisé, N, Verny, C, Brice, A, Sherman, DL, Brophy, PJ, LeGuern, E, Delague, V, Bareil, C, Megarbane, A, Claustres, M	Hum. Mol. Genet.	2001
24675079	Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping Han, H, Kursula, P	J. Biol. Chem.	2014
11394999	EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression Nagarajan, R, Svaren, J, Le, N, Araki, T, Watson, M, Milbrandt, J	Neuron	2001