CNTNAP1 Membrane Protein Introduction

Introduction of CNTNAP1

CNTNAP1 is encoded by the CNTNAP1 gene and is also known as contactin-associated protein 1, Caspr1 and paranodin. It belongs to the Caspr or CATNAP family, which is not only involved in the formation of myelinated axons but also participates in maintaining the stability of adjacent connections. It is one of the five subtypes of CATNAP family proteins, CNTNAP1 (Caspr1), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5). CNTNAP1 is a single-pass transmembrane protein, was originally identified in neurons by its interaction with contactin protein.

Function of CNTNAP1 Membrane Protein

CNTNAP1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. CNTNAP1 is localized in the paranodal region and has a role in the generation and maintenance of paranodal junctions in myelinated axons. It forms a complex with contactin and NFASC-155 (NF-155), acts as a barrier between the nodes of Ranvier and internodes, and is involved in the propagation of action potentials and mediation of signal transport. Furthermore, a recent study indicated that CNTNAP1 may mediate the timing of neuron and astrocyte differentiation in neural progenitor cells. The expression of CNTNAP1 has also been associated with certain neurodegenerative diseases and may represent a therapeutic target for treatment. CNTNAP1 is also reported to act as a receptor of bacterial virulence factor IbeA for E. coli penetration through the blood-brain barrier and neuronal CNTNAP1 is exploited by IbeA for the E. coli invasion into neurons leading to neuronal apoptosis.

Fig.1 Proposed model of CNTNAP1(Caspr1) in the intervention of E. coli meningitis (Zhao, 2018).

Application of CNTNAP1 Membrane Protein in Literature

1. Zhao W.D., et al. Caspr1 is a host receptor for meningitis-causing Escherichia coli. Nature Communications. 2018, 9(1):2296. PubMed ID: 29895952
   
   

   The results of this article indicate that E. coli exploits Caspr1 (CNTNAP1) as a host receptor for penetration of BBB resulting in meningitis, and that Caspr1 might be a useful target for prevention or therapy of E. coli meningitis.

2. Zou Y., et al. Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases. Neural Regeneration Research. 2017, 12(9):1551-1558. PubMed ID: 29090003
   
   

   The authors in this article analyze the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis and the effects of CNTNAP1 on disease diagnosis and treatment need further investigation.

3. Santos S.D., et al. Contactin-associated Protein 1 (Caspr1) Regulates the Traffic and Synaptic Content of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA)-type Glutamate Receptors. The Journal of Biological Chemistry. 2012, 287(9):6868-6877. PubMed ID: 22223644
   
   

   This article reveals that CNTNAP1 is present in synapses and interacts with AMPA receptors in brain synaptic fractions and coexpression of CNTNAP1 with GluA1 increases the amplitude of glutamate-evoked currents. Hence, CNTNAP1 is a regulator of the trafficking of AMPA receptors to synapses.

4. Vallat J.M., et al. Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region. J. Neuropathol. Exp. Neurol. 2016, 75(12):1155-1159. PubMed ID: 27818385
   
   

   This article suggests that CNTNAP1 is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-glial junctions.

5. Mehta P., et al. Novel Mutation in CNTNAP1 results in Congenital Hypomyelinating Neuropathy. Muscle Nerve. 2017, 55(5):761-765. PubMed ID: 27668699
   
   

   This article identifies a novel CNTNAP1 homozygous missense mutation (Arg388Pro) in the proband, and both parents were carriers. Molecular modeling suggests that this variant disrupts a β-strand to cause an unstable structure and likely significant changes in protein function.

CNTNAP1 Preparation Options

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Reference

1. Zhao W.D., et al. (2018) Caspr1 is a host receptor for meningitis-causing Escherichia coli. Nature Communications. 9(1):2296.

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