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

From: All-you-can-eat: autophagy in neurodegeneration and neuroprotection

Gene
(Alias)
Protein function Knockout/knockdown OE/TG ES/M @ IMSR Neuronal phenotype after k.o./k.d.
(Animal model)
K.o. embryonic lethal
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)
  1. Examples of model organism with knockout, knockdown, or overexpression of autophagy genes and the corresponding neuronal phenotype. Approved human gene names are used http://www.genenames.org, in addition commonly used aliases are provided. # While non-neuronal Atg5 and Atg7 k.o. mice survive birth, they die within one day postnatal. (MM): M. musculus; (DM): D. melanogaster; (CE): C. elegans; (OE): overexpression; (ES): embryonic knockout stem cell; (M): mouse line; (TG): transgenic; (GT): gene-trap; (MUT): targeted mutation; (IMSR): knockout ES/mice available through the International Mouse Strain Resource http://www.informatics.jax.org/imsr/index.jsp; (*): neuronal tissue examined; (n.a.): not available.