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The tau code.

Avila J - Front Aging Neurosci (2009)

Bottom Line: In this short review, I will focus on how a unique tau gene may produce many tau isoforms through alternative splicing and how the phosphorylation of these isoforms by different kinases may affect their activity and behaviour.Indeed, each of the different tau isoforms may play a distinct role under both physiological and pathological conditions.Thus, I will discuss whether a tau code exists that might explain the involvement of different tau isoforms in different cellular functions.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid Madrid, Spain.

ABSTRACT
In this short review, I will focus on how a unique tau gene may produce many tau isoforms through alternative splicing and how the phosphorylation of these isoforms by different kinases may affect their activity and behaviour. Indeed, each of the different tau isoforms may play a distinct role under both physiological and pathological conditions. Thus, I will discuss whether a tau code exists that might explain the involvement of different tau isoforms in different cellular functions.

No MeSH data available.


Related in: MedlinePlus

Tau phosphorylation in tauopathies. (A) More than 40 residues of the different tau isoforms can be modified in Alzheimer disease (AD). Some of these sites are modified by GSK3, and the modified serine residues (184, 198, 199, 202, 210, 214, 235, 237, 258, 262, 289, 356, 396, 400, 404, 409, 412, 413, 416) or threonine residues (69, 175, 181, 212, 217, 231, 414) have been localized within the tau molecule (Hanger et al., 2009). In addition, there are three possible tyrosine residues (18, 29, 394) that could be modified in AD, the main candidates each located in the amino terminal domain. Fewer residues modified by GSK3 have been identified in tau from progressive supracellular palsy (PSP). (B) These and other phosphorylation events can regulate the interaction of tau protein with the cell membrane, microtubules, other proteins or its self association. The circles indicate the localization of the phosphorylated residues that prevent interactions (Ser 199-202) with the cell membrane, (Ser 262) with microtubules, or (Ser 396-404) with muscarine receptors. Also, when the serines (396-404) are phosphorylated the interaction of phospho tau with α-synuclein and GSK3β is favoured. (C) Scheme showing the six CNS tau isoforms. Three 3R and three 4R tau isoforms.)
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Figure 1: Tau phosphorylation in tauopathies. (A) More than 40 residues of the different tau isoforms can be modified in Alzheimer disease (AD). Some of these sites are modified by GSK3, and the modified serine residues (184, 198, 199, 202, 210, 214, 235, 237, 258, 262, 289, 356, 396, 400, 404, 409, 412, 413, 416) or threonine residues (69, 175, 181, 212, 217, 231, 414) have been localized within the tau molecule (Hanger et al., 2009). In addition, there are three possible tyrosine residues (18, 29, 394) that could be modified in AD, the main candidates each located in the amino terminal domain. Fewer residues modified by GSK3 have been identified in tau from progressive supracellular palsy (PSP). (B) These and other phosphorylation events can regulate the interaction of tau protein with the cell membrane, microtubules, other proteins or its self association. The circles indicate the localization of the phosphorylated residues that prevent interactions (Ser 199-202) with the cell membrane, (Ser 262) with microtubules, or (Ser 396-404) with muscarine receptors. Also, when the serines (396-404) are phosphorylated the interaction of phospho tau with α-synuclein and GSK3β is favoured. (C) Scheme showing the six CNS tau isoforms. Three 3R and three 4R tau isoforms.)

Mentions: Up to 40 residues have been seen to be modified in tau protein isolated from the brain of AD patients (Hanger et al., 2009), with GSK3 being identified as the kinase that could phosphorylate more sites in the tau molecule (Figure 1). However, tau phosphorylation in AD could result from the phosphorylation of different tau isoforms modified at different sites, rather than the modification of the 40 sites in a single tau molecule (Hernandez et al., 2003).


The tau code.

Avila J - Front Aging Neurosci (2009)

Tau phosphorylation in tauopathies. (A) More than 40 residues of the different tau isoforms can be modified in Alzheimer disease (AD). Some of these sites are modified by GSK3, and the modified serine residues (184, 198, 199, 202, 210, 214, 235, 237, 258, 262, 289, 356, 396, 400, 404, 409, 412, 413, 416) or threonine residues (69, 175, 181, 212, 217, 231, 414) have been localized within the tau molecule (Hanger et al., 2009). In addition, there are three possible tyrosine residues (18, 29, 394) that could be modified in AD, the main candidates each located in the amino terminal domain. Fewer residues modified by GSK3 have been identified in tau from progressive supracellular palsy (PSP). (B) These and other phosphorylation events can regulate the interaction of tau protein with the cell membrane, microtubules, other proteins or its self association. The circles indicate the localization of the phosphorylated residues that prevent interactions (Ser 199-202) with the cell membrane, (Ser 262) with microtubules, or (Ser 396-404) with muscarine receptors. Also, when the serines (396-404) are phosphorylated the interaction of phospho tau with α-synuclein and GSK3β is favoured. (C) Scheme showing the six CNS tau isoforms. Three 3R and three 4R tau isoforms.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874412&req=5

Figure 1: Tau phosphorylation in tauopathies. (A) More than 40 residues of the different tau isoforms can be modified in Alzheimer disease (AD). Some of these sites are modified by GSK3, and the modified serine residues (184, 198, 199, 202, 210, 214, 235, 237, 258, 262, 289, 356, 396, 400, 404, 409, 412, 413, 416) or threonine residues (69, 175, 181, 212, 217, 231, 414) have been localized within the tau molecule (Hanger et al., 2009). In addition, there are three possible tyrosine residues (18, 29, 394) that could be modified in AD, the main candidates each located in the amino terminal domain. Fewer residues modified by GSK3 have been identified in tau from progressive supracellular palsy (PSP). (B) These and other phosphorylation events can regulate the interaction of tau protein with the cell membrane, microtubules, other proteins or its self association. The circles indicate the localization of the phosphorylated residues that prevent interactions (Ser 199-202) with the cell membrane, (Ser 262) with microtubules, or (Ser 396-404) with muscarine receptors. Also, when the serines (396-404) are phosphorylated the interaction of phospho tau with α-synuclein and GSK3β is favoured. (C) Scheme showing the six CNS tau isoforms. Three 3R and three 4R tau isoforms.)
Mentions: Up to 40 residues have been seen to be modified in tau protein isolated from the brain of AD patients (Hanger et al., 2009), with GSK3 being identified as the kinase that could phosphorylate more sites in the tau molecule (Figure 1). However, tau phosphorylation in AD could result from the phosphorylation of different tau isoforms modified at different sites, rather than the modification of the 40 sites in a single tau molecule (Hernandez et al., 2003).

Bottom Line: In this short review, I will focus on how a unique tau gene may produce many tau isoforms through alternative splicing and how the phosphorylation of these isoforms by different kinases may affect their activity and behaviour.Indeed, each of the different tau isoforms may play a distinct role under both physiological and pathological conditions.Thus, I will discuss whether a tau code exists that might explain the involvement of different tau isoforms in different cellular functions.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid Madrid, Spain.

ABSTRACT
In this short review, I will focus on how a unique tau gene may produce many tau isoforms through alternative splicing and how the phosphorylation of these isoforms by different kinases may affect their activity and behaviour. Indeed, each of the different tau isoforms may play a distinct role under both physiological and pathological conditions. Thus, I will discuss whether a tau code exists that might explain the involvement of different tau isoforms in different cellular functions.

No MeSH data available.


Related in: MedlinePlus