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Table 2 Proteins possibly involved in microtubule breakdown after Aβ insult

From: Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer Disease and Hereditary Spastic Paraplegia

Protein (gene name)

Physiological function

Pathological function

Genetic loci [12]

Tau (MAPT)

microtubule stabilization, axonal outgrowth

aberrant transport of proteins (e.g. TTLL6, fyn), f-actin dissassembly

17q21.31

TTLL6 (TTLL6)

polyGlu chain elongation, preferentially at α-tubulin

excessive polyglutamylation leading to aberrant spastin activation

17q21.32

spastin (SPAST)

microtubule dynamics, transport of membrane vesicles/endosomes, dendrite branching

microtubule breakdown

2p22.3

MARK1,2,3,4 (MARK1,2,3,4)

transport regulation via phosphorylation of MAPs

aberrant phosphorylation of MAPs resulting in decreased microtubule protection

1:1q41

2:11q13.1

3:14q32.32

4:19q13.32

TTLL11 (TTLL11)

polyGlu chain elongation, preferentially at α-tubulin

similar action as TTLL6 (but path. role not yet shown)

9q33.2

TTLL1 (TTLL1)

polyGlu chain initiation at α- and β- tubulin

required for action of TTLL6 and TTLL11 (but path. role not yet shown)

22q13.2

CCP1,4,5,6 (AGTPBP1, AGBL1, AGBL5, AGBL4)

remove (poly)glutamate side chains from microtubules

impaired function could result in increased polyglutamylation (but path. role not yet shown)

1: 9q21.33

4: 15q25.3

5: 2p23.3

6: 1p33

Katanin (KATNA1)

microtubule severing, axon branching

also activated by polyglutamylation of microtubules (but path. role not yet shown)

6q24.3

Fidgetin (FIGN)

microtubule severing, mitosis regulation

path. role not shown

2q24.3