Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy

How cellular stresses up-regulate autophagy is not fully understood. One potential regulator is the Drosophila melanogaster protein Acinus (Acn), which is necessary for autophagy induction and triggers excess autophagy when overexpressed. We show that cell type–specific regulation of Acn depends on proteolysis by the caspase Dcp-1. Basal Dcp-1 activity in developing photoreceptors is sufficient for this cleavage without a need for apoptosis to elevate caspase activity. On the other hand, Acn was stabilized by loss of Dcp-1 function or by the presence of a mutation in Acn that eliminates its conserved caspase cleavage site. Acn stability also was regulated by AKT1-mediated phosphorylation. Flies that expressed stabilized forms of Acn, either the phosphomimetic AcnS641,731D or the caspase-resistant AcnD527A, exhibited enhanced basal autophagy. Physiologically, these flies showed improvements in processes known to be autophagy dependent, including increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged life span. These data indicate that AKT1 and caspase-dependent regulation of Acn stability adjusts basal autophagy levels.

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Cell type-specific regulation of amniotic fibronectin expression by Glucocorticoid (GC): Conservation of GC responsiveness in humans and non-human primates

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86698-1 ◽

1998 ◽

Vol 5 (1) ◽

pp. 191A-191A

Author(s):

Y MA ◽

A BUNIM ◽

D GIUSSANI ◽

P NATHANIELSZ ◽

C LOCKWOOD ◽

...

Keyword(s):

Cell Type ◽

Fibronectin Expression ◽

Cell Type Specific ◽

Specific Regulation

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Faculty Opinions recommendation of Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1119471.580547 ◽

2008 ◽

Author(s):

Guoping Feng ◽

Jonathan Ting

Keyword(s):

Antipsychotic Drugs ◽

Cell Type ◽

Cell Type Specific ◽

Specific Regulation

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Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

Molecular Psychiatry ◽

10.1038/s41380-021-01217-8 ◽

2021 ◽

Author(s):

Hee-Dae Kim ◽

Jing Wei ◽

Tanessa Call ◽

Nicole Teru Quintus ◽

Alexander J. Summers ◽

...

Keyword(s):

Nucleus Accumbens ◽

Molecular Mechanisms ◽

Cell Types ◽

Current Treatment ◽

Specific Cell ◽

Excitatory Synapses ◽

Cell Type ◽

Cell Type Specific ◽

Specific Regulation ◽

Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

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Cell-type-specific regulation of raft-associated Akt signaling

Cell Death and Disease ◽

10.1038/cddis.2011.28 ◽

2011 ◽

Vol 2 (4) ◽

pp. e145-e145 ◽

Cited By ~ 13

Author(s):

Y Liu ◽

G Yang ◽

X Bu ◽

G Liu ◽

J Ding ◽

...

Keyword(s):

Akt Signaling ◽

Cell Type ◽

Cell Type Specific ◽

Specific Regulation

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Gene, stimulus and cell-type specific regulation of activator protein-1 in mesangial cells by lipopolysaccharide and cytokines

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression ◽

10.1016/s0167-4781(00)00089-0 ◽

2000 ◽

Vol 1492 (1) ◽

pp. 100-107 ◽

Cited By ~ 10

Author(s):

Rachel L Granger ◽

Timothy R Hughes ◽

Dipak P Ramji

Keyword(s):

Mesangial Cells ◽

Activator Protein 1 ◽

Cell Type ◽

Activator Protein ◽

Cell Type Specific ◽

Specific Regulation

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Periaqueductal efferents to dopamine and GABA neurons of the VTA

10.1101/117416 ◽

2017 ◽

Cited By ~ 1

Author(s):

Niels R. Ntamati ◽

Meaghan Creed ◽

Christian Lüscher

Keyword(s):

Functional Analysis ◽

Ventral Tegmental Area ◽

Periaqueductal Gray ◽

Retrograde Tracing ◽

The Other ◽

Projection Neurons ◽

Cell Type ◽

Gaba Neurons ◽

Other Hand ◽

Cell Type Specific

AbstractNeurons in the periaqueductal gray (PAG) modulate threat responses and nociception. Activity in the ventral tegmental area (VTA) on the other hand can cause reinforcement and aversion. While in many situations these behaviors are related, the anatomical substrate of a crosstalk between the PAG and VTA remains poorly understood. Here we describe the anatomical and electrophysiological organization of the VTA-projecting PAG neurons. Using rabies-based, cell type-specific retrograde tracing, we observed that PAG to VTA projection neurons are evenly distributed along the rostro-caudal axis of the PAG, but concentrated in its posterior and ventrolateral segments. Optogenetic projection targeting demonstrated that the PAG-to-VTA pathway is predominantly excitatory and targets similar proportions of Ih-expressing VTA DA and GABA neurons. Taken together, these results set the framework for functional analysis of the interplay between PAG and VTA in the regulation of reward and aversion.

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