Table 2 Neuronal phenotype of autophagy related knockout/knockdown animal models.

ULK1

(ATG1)

Ser/Thr protein kinase (regulation and vesicle formation)

[107, 112, 113] *

[97, 99, 100, 131, 132, 135, 141, 145]

[140] (OE)

ES

M (GT)

Impaired endocytosis of nerve growth factor, excessive axon arborization, stunted axon elongation (MM)

Paralysis, aberrant axon growth, abnormal vesicles, arrested differentiation (CE)

Yes (DM)

ATG3

Ubiquitin-conjugating-like enzyme (attaches MAP1LC3 to PE)

[111, 143]

n.a.

Not reported

Yes (DM)

ATG4

Cystein protease (cleaves C-terminus of MAP1LC3 for conjugation)

[90, 144]

ES

M (GT/TG)

Not reported

Yes (CE)

ATG5

Unknown (conjugates to ATG12, binds ATG16)

[60] *

[91, 130, 141]

ES

M (MUT)

Progressive motor deficits, accumulation of inclusion bodies, neurodegeneration, aberrant vacuoles in Purkinje cells (MM)

No # (DM/MM)

BECN1

(ATG6)

Unknown (part of class III PI3K complex, anchor protein, autophagy initiation)

[59] *

[97, 116, 124, 137, 146]

[119] (TG)

M (TG)

Neurodegeneration, lysosomal abnormalities (MM)

Yes (MM/CE/DM)

PIK3C3

(VPS34)

Class III PI3K complex (forms complex with BECN1/PIK3R4/AMBRA1/UVRAG, autophagy initiation)

[123, 142] *

[114, 126]

ES

Abnormal protein aggregation, abnormal locomotion (CE)

Yes (CE)

PIK3R4

(VPS15, P150)

Ser/Thr protein kinase (forms a complex with and activates PIK3C3)

[134]

ES

Not reported

Yes (DM)

AMBRA1

Unknown (component of the class III PI3K complex)

[83] *

ES

Neural tube defects, polyU aggregates, unbalanced cell proliferation, cell death (MM)

Yes (MM)

ATG7

Ubiquitin-activating-like enzyme (activates MAP1LC3 and ATG12 for conjugation)

[61, 123, 129] *

[124, 125, 127, 128, 136, 141]

ES

Behavioral deficits, neuronal loss, polyU inclusions, axonal dystrophy, axonal terminal degeneration (MM)

PolyU aggregates, neuronal degeneration (DM)

Abnormal protein aggregation (CE)

No # (DM/MM)

MAP1LC3

(LC3)

Unknown (similarity with ubiquitin, part of autophagosomal membrane)

[123, 145] *

[79, 97]

[27] (TG)

ES

M (TG)

Abnormal protein aggregation (CE)

Yes (CE)

No (MM)

ATG12

Unknown (similarity with ubiquitin, conjugated to ATG5)

[123] *

n.a.

Abnormal protein aggregation (CE)

Unknown

CHMP4B

(SNF7-2)

Unknown (part of the ESCRT-III complex, involved in surface receptor degradation, formation of MVBs and autophagosomes)

[85, 115, 138]

ES

Dendritic and axonal branching impaired, dendritic retraction, reduced cell viability, autophagosomes accumulate, increased htt toxicity (DM)

Yes (MM)

HSPA8

(HSC70)

Chaperone (recognizes CMA motif, lysosomal translocation)

[121, 139] *

[120] (OE)

ES

Impaired transmitter release, o.e. rescues α-synuclein pathology, Bolwig's nerve projection abnormalities (DM)

Yes (DM)

LAMP2

Unknown (Lysosomal membrane glyco-protein, forms complex with HSPA8)

[40]

ES

Not reported

No (MM)