Редактирование: MAP1A

Microtubule-associated protein 1A (MAP-1A) (Proliferation-related protein p80) [Contains: MAP1A heavy chain; MAP1 light chain LC2] [MAP1L]

==Publications==

{{medline-entry
|title=SerThr-PhosphoProteome of Brain from Aged [[PINK1]]-KO A53T-[[SNCA]] Mice Reveals pT1928-[[MAP1B]] and pS3781-[[ANK2]] Deficits, as Hub between Autophagy and Synapse Changes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31277379
|abstract=Hereditary Parkinson's disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein ([[SNCA]]) as stressor or the autosomal recessive deficiency of [[PINK1]] Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of [[PINK1]]-knockout with overexpression of [[SNCA]]  in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As an exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in [[MAP1B]], a microtubule-associated protein, and a similar reduction of phosphoSer3781 in [[ANK2]], an interactor of microtubules. [[MAP1B]] depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension, and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was also detected for other microtubule and microfilament factors, namely [[MAP2]] , [[MARK1]] , [[MAP1A]] , [[KIF1A]] , 4.1N , 4.1G , and [[ADD2]] . While the [[MAP1B]] heavy chain supports regeneration and growth cones, its light chain assists [[DAPK1]]-mediated autophagy. Interestingly, relevant phosphorylation decreases of [[DAPK2]] , [[VPS13D]] , and [[VPS13C]]  in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM [[C2]] domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of [[ANK2]]/[[MAP1B]] expression on [[PINK1]] levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that [[MAP1B]]/[[ANK2]] phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in [i]Drosophila melanogaster[/i] that the [[MAP1B]] ortholog futsch in the presynapse is a primary target of the PARK8 protein [[LRRK2]], and on a report that [[MAP1B]] is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, [i][[ANK2]][/i] gene locus variants are associated with the risk of PD, [[ANK2]] interacts with [[PINK1]]/Parkin-target proteins such as MIRO1 or [[ATP1A2]], and [[ANK2]]-derived peptides are potent inhibitors of autophagy.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Ankyrins
* Autophagy
* Brain
* Mice, Knockout
* Mice, Mutant Strains
* Microtubule-Associated Proteins
* Microtubules
* Phosphoproteins
* Phosphorylation
* Phosphoserine
* Phosphothreonine
* Protein Domains
* Protein Kinases
* Proteome
* Synapses
* alpha-Synuclein
|keywords=* PINK1
* Parkinson’s disease
* alpha-synuclein
* autophagy
* brain phosphorylome
* microtubular cytoskeleton
* synaptic signaling
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651490
}}
{{medline-entry
|title=Loss of MAP function leads to hippocampal synapse loss and deficits in the Morris Water Maze with aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24849348
|abstract=Hyperphosphorylation and accumulation of tau aggregates are prominent features in tauopathies, including Alzheimer's disease, but the impact of loss of tau function on synaptic and cognitive deficits remains poorly understood. We report that old (19-20 months; OKO) but not middle-aged (8-9 months; MKO) tau knock-out mice develop Morris Water Maze (MWM) deficits and loss of hippocampal acetylated α-tubulin and excitatory synaptic proteins. Mild motor deficits and reduction in tyrosine hydroxylase ([[TH]]) in the substantia nigra were present by middle age, but did not affect MWM performance, whereas OKO mice showed MWM deficits paralleling hippocampal deficits. Deletion of tau, a microtubule-associated protein (MAP), resulted in increased levels of [[MAP1A]], [[MAP1B]], and [[MAP2]] in MKO, followed by loss of [[MAP2]] and [[MAP1B]] in OKO. Hippocampal synaptic deficits in OKO mice were partially corrected with dietary supplementation with docosahexaenoic acid (DHA) and both MWM and synaptic deficits were fully corrected by combining DHA with α-lipoic acid (ALA), which also prevented [[TH]] loss. DHA or DHA/ALA restored phosphorylated and total GSK3β and attenuated hyperactivation of the tau C-Jun N-terminal kinases (JNKs) while increasing [[MAP1B]], dephosphorylated (active) [[MAP2]], and acetylated α-tubulin, suggesting improved microtubule stability and maintenance of active compensatory MAPs. Our results implicate the loss of MAP function in age-associated hippocampal deficits and identify a safe dietary intervention, rescuing both MAP function and [[TH]] in OKO mice. Therefore, in addition to microtubule-stabilizing therapeutic drugs, preserving or restoring compensatory MAP function may be a useful new prevention strategy. 
|mesh-terms=* Aging
* Alzheimer Disease
* Animals
* Disease Models, Animal
* Docosahexaenoic Acids
* Gene Expression Regulation
* Hippocampus
* Learning Disabilities
* Maze Learning
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Movement Disorders
* Psychomotor Performance
* Reaction Time
* Substantia Nigra
* Synapses
* Thioctic Acid
* tau Proteins
|keywords=* Alzheimer's disease
* MAPs
* Morris Water Maze
* knock-out
* synaptic markers
* tau
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028492
}}