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Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B.

Duflocq A, Chareyre F, Giovannini M, Couraud F, Davenne M - BMC Biol. (2011)

Bottom Line: We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins.We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS.Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM UMRS 952, 9 Quai St Bernard, F-75005, Paris, France.

ABSTRACT

Background: The axon initial segment (AIS) plays a crucial role: it is the site where neurons initiate their electrical outputs. Its composition in terms of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels, as well as its length and localization determine the neuron's spiking properties. Some neurons are able to modulate their AIS length or distance from the soma in order to adapt their excitability properties to their activity level. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a neuron's excitability properties and ability to display such plasticity mechanisms. If the myelin sheath starts immediately after the AIS, another question then arises as to how would the axon be organized at its first myelin attachment site; since AISs are different from nodes of Ranvier, would this particular axonal region resemble a hemi-node of Ranvier?

Results: We have characterized the AIS of mouse somatic motor neurons. In addition to constant determinants of excitability properties, we found heterogeneities, in terms of AIS localization and Nav composition. We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins. We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS. Their expression in the AIS and JXP-AIS is independent from transient axonal glycoprotein-1 (TAG-1)/Caspr2, in contrast to juxtaparanodes, and independent from PSD-93. Data from mice lacking the cytoskeletal linker protein 4.1B show that this protein is necessary to form the Caspr+ para-AIS barrier, ensuring the compartmentalization of Kv1 channels and the segregation of the AIS, para-AIS and JXP-AIS.

Conclusions: α Motor neurons have heterogeneous AISs, which underlie different spiking properties. However, they all have a para-AIS and a JXP-AIS contiguous to their AIS, where the myelin sheath begins, which might limit some AIS plasticity. Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

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Summary diagram. (A) Localization and molecular composition of the axon initial segment (AIS), para-AIS and juxtapara (JXP)-AIS in α motor neurons (MNs). α MNs have either a soma-derived AIS (85% of α MNs) or a dendrite-derived AIS (15%). From the MNs with a soma-derived AIS, 79% of them express voltage-gated sodium channel (Nav)1.1 and Nav1.6, while 20.2% express Nav1.6 only. The remaining AIS, Para-AIS and JXP-AIS proteins were found in 100% of α MNs: KCNQ2 throughout the AIS only, while voltage-gated potassium channel (Kv)1.1/Kv1.2/Kvβ2, PSD-93 and contactin-associated protein-like 2 (Caspr2) in the distal AIS and JXP-AIS, Caspr in the para-AIS, and protein 4.1B in the para-AIS, JXP-AIS and the internode. (B) Kv1 channels are expressed in the AIS and JXP-AIS by mechanisms independent of transient axonal glycoprotein-1 (TAG-1)/Caspr2 and PSD-93, while protein 4.1B was shown to control Caspr expression in the para-AIS and thus the proper exclusion of Kv1 channels from the para-AIS and the proper segregation of AnkG and Caspr from one another.
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Figure 11: Summary diagram. (A) Localization and molecular composition of the axon initial segment (AIS), para-AIS and juxtapara (JXP)-AIS in α motor neurons (MNs). α MNs have either a soma-derived AIS (85% of α MNs) or a dendrite-derived AIS (15%). From the MNs with a soma-derived AIS, 79% of them express voltage-gated sodium channel (Nav)1.1 and Nav1.6, while 20.2% express Nav1.6 only. The remaining AIS, Para-AIS and JXP-AIS proteins were found in 100% of α MNs: KCNQ2 throughout the AIS only, while voltage-gated potassium channel (Kv)1.1/Kv1.2/Kvβ2, PSD-93 and contactin-associated protein-like 2 (Caspr2) in the distal AIS and JXP-AIS, Caspr in the para-AIS, and protein 4.1B in the para-AIS, JXP-AIS and the internode. (B) Kv1 channels are expressed in the AIS and JXP-AIS by mechanisms independent of transient axonal glycoprotein-1 (TAG-1)/Caspr2 and PSD-93, while protein 4.1B was shown to control Caspr expression in the para-AIS and thus the proper exclusion of Kv1 channels from the para-AIS and the proper segregation of AnkG and Caspr from one another.

Mentions: We indeed found that, in contrast to γ MNs which all have a soma-derived AIS, α MNs have either a soma-derived or a dendrite-derived AIS (Figure 11A). To our knowledge such dendrite-derived axons in MNs have only been alluded to previously [43], but never described and quantified. The dendritic origin of the axon, reported in several neuronal types, may have a functional impact on the neuron's integrative properties. The axon-bearing dendrite, not separated from the AIS by the soma, is privileged in its ability to influence action potential initiation and synapses impinging on its proximal part, between the soma and the AIS, may act as gating synapses regulating how inputs from the soma and other dendrites might influence the AIS [44-46]. We also found that the distance from the soma to the AIS differs among MNs, and is longer in average for dendrite-derived AISs, which are thus more isolated from somatodendritic synaptic inputs and, as a consequence, might be less excitable [2,3].


Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B.

Duflocq A, Chareyre F, Giovannini M, Couraud F, Davenne M - BMC Biol. (2011)

Summary diagram. (A) Localization and molecular composition of the axon initial segment (AIS), para-AIS and juxtapara (JXP)-AIS in α motor neurons (MNs). α MNs have either a soma-derived AIS (85% of α MNs) or a dendrite-derived AIS (15%). From the MNs with a soma-derived AIS, 79% of them express voltage-gated sodium channel (Nav)1.1 and Nav1.6, while 20.2% express Nav1.6 only. The remaining AIS, Para-AIS and JXP-AIS proteins were found in 100% of α MNs: KCNQ2 throughout the AIS only, while voltage-gated potassium channel (Kv)1.1/Kv1.2/Kvβ2, PSD-93 and contactin-associated protein-like 2 (Caspr2) in the distal AIS and JXP-AIS, Caspr in the para-AIS, and protein 4.1B in the para-AIS, JXP-AIS and the internode. (B) Kv1 channels are expressed in the AIS and JXP-AIS by mechanisms independent of transient axonal glycoprotein-1 (TAG-1)/Caspr2 and PSD-93, while protein 4.1B was shown to control Caspr expression in the para-AIS and thus the proper exclusion of Kv1 channels from the para-AIS and the proper segregation of AnkG and Caspr from one another.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3198992&req=5

Figure 11: Summary diagram. (A) Localization and molecular composition of the axon initial segment (AIS), para-AIS and juxtapara (JXP)-AIS in α motor neurons (MNs). α MNs have either a soma-derived AIS (85% of α MNs) or a dendrite-derived AIS (15%). From the MNs with a soma-derived AIS, 79% of them express voltage-gated sodium channel (Nav)1.1 and Nav1.6, while 20.2% express Nav1.6 only. The remaining AIS, Para-AIS and JXP-AIS proteins were found in 100% of α MNs: KCNQ2 throughout the AIS only, while voltage-gated potassium channel (Kv)1.1/Kv1.2/Kvβ2, PSD-93 and contactin-associated protein-like 2 (Caspr2) in the distal AIS and JXP-AIS, Caspr in the para-AIS, and protein 4.1B in the para-AIS, JXP-AIS and the internode. (B) Kv1 channels are expressed in the AIS and JXP-AIS by mechanisms independent of transient axonal glycoprotein-1 (TAG-1)/Caspr2 and PSD-93, while protein 4.1B was shown to control Caspr expression in the para-AIS and thus the proper exclusion of Kv1 channels from the para-AIS and the proper segregation of AnkG and Caspr from one another.
Mentions: We indeed found that, in contrast to γ MNs which all have a soma-derived AIS, α MNs have either a soma-derived or a dendrite-derived AIS (Figure 11A). To our knowledge such dendrite-derived axons in MNs have only been alluded to previously [43], but never described and quantified. The dendritic origin of the axon, reported in several neuronal types, may have a functional impact on the neuron's integrative properties. The axon-bearing dendrite, not separated from the AIS by the soma, is privileged in its ability to influence action potential initiation and synapses impinging on its proximal part, between the soma and the AIS, may act as gating synapses regulating how inputs from the soma and other dendrites might influence the AIS [44-46]. We also found that the distance from the soma to the AIS differs among MNs, and is longer in average for dendrite-derived AISs, which are thus more isolated from somatodendritic synaptic inputs and, as a consequence, might be less excitable [2,3].

Bottom Line: We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins.We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS.Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM UMRS 952, 9 Quai St Bernard, F-75005, Paris, France.

ABSTRACT

Background: The axon initial segment (AIS) plays a crucial role: it is the site where neurons initiate their electrical outputs. Its composition in terms of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels, as well as its length and localization determine the neuron's spiking properties. Some neurons are able to modulate their AIS length or distance from the soma in order to adapt their excitability properties to their activity level. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a neuron's excitability properties and ability to display such plasticity mechanisms. If the myelin sheath starts immediately after the AIS, another question then arises as to how would the axon be organized at its first myelin attachment site; since AISs are different from nodes of Ranvier, would this particular axonal region resemble a hemi-node of Ranvier?

Results: We have characterized the AIS of mouse somatic motor neurons. In addition to constant determinants of excitability properties, we found heterogeneities, in terms of AIS localization and Nav composition. We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins. We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS. Their expression in the AIS and JXP-AIS is independent from transient axonal glycoprotein-1 (TAG-1)/Caspr2, in contrast to juxtaparanodes, and independent from PSD-93. Data from mice lacking the cytoskeletal linker protein 4.1B show that this protein is necessary to form the Caspr+ para-AIS barrier, ensuring the compartmentalization of Kv1 channels and the segregation of the AIS, para-AIS and JXP-AIS.

Conclusions: α Motor neurons have heterogeneous AISs, which underlie different spiking properties. However, they all have a para-AIS and a JXP-AIS contiguous to their AIS, where the myelin sheath begins, which might limit some AIS plasticity. Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

Show MeSH
Related in: MedlinePlus