FAM81A is a postsynaptic protein that regulates the condensation of postsynaptic proteins via liquid-liquid phase separation.

Proteome analyses of the postsynaptic density (PSD), a proteinaceous specialization beneath the postsynaptic membrane of excitatory synapses, have identified several thousands of proteins. While proteins with predictable functions have been well studied, functionally uncharacterized proteins are mostly overlooked. In this study, we conducted a comprehensive meta-analysis of 35 PSD proteome datasets, encompassing a total of 5,869 proteins.

The blues and rhythm.

Most organisms, including humans, show daily rhythms in many aspects of physiology and behavior, and abnormalities in the rhythms are potential risk factors for various diseases. Mood disorders such as depression are no exception. Accumulating evidence suggests strong associations between circadian disturbances and the development of depression.

Spinocerebellar ataxia type 14 caused by a nonsense mutation in the PRKCG gene.

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia with myoclonus, dystonia, spasticity, and rigidity. Although missense mutations and a deletion mutation have been found in the protein kinase C gamma (PRKCG) gene encoding protein kinase C γ (PKCγ) in SCA14 families, a nonsense mutation has not been reported. The patho-mechanisms underlying SCA14 remain poorly understood.

Validation of Anti-CSPα, SNAP25, Tyrosine Hydroxylase, Ubiquitin, Cleaved Caspase 3, and pSer PKC Motif Antibodies for Utilization in Western Blotting.

There are many commercial antibodies with little information provided by their suppliers as to their reliability. Accordingly, commercial antibodies require proper validation before being used in scientific research. In this study, we validated several commercial antibodies, including anti-CSPα, SNAP25, tyrosine hydroxylase, ubiquitin, cleaved caspase 3, and pSer PKC motif.

The Role of Cysteine String Protein α Phosphorylation at Serine 10 and 34 by Protein Kinase Cγ for Presynaptic Maintenance.

Protein kinase Cγ (PKCγ) knock-out (KO) animals exhibit symptoms of Parkinson's disease (PD), including dopaminergic neuronal loss in the substantia nigra. However, the PKCγ substrates responsible for the survival of dopaminergic neurons have not yet been elucidated. Previously, we found 10 potent substrates in the striatum of PKCγ-KO mice.

The Development of Screening Methods to Identify Drugs to Limit ER Stress Using Wild-type and Mutant Serotonin Transporter.

The function of the serotonin transporter (SERT) is regulated by its membrane trafficking. Previously, we showed that the C-terminus-deleted mutant of SERT (SERTΔCT) exhibited an aberrant membrane trafficking and subsequent retention at the endoplasmic reticulum (ER). In addition, we found that proteasome inhibitor-induced ER stress resulted in the impairment of SERT membrane trafficking and retention of SERT at the ER, an impairment very similar to that of SERTΔCT.

The Toll-like receptor 4-activated neuroprotective microglia subpopulation survives via granulocyte macrophage colony-stimulating factor and JAK2/STAT5 signaling.

Toll-like receptor (TLR) 4 mediates inflammation and is also known to trigger apoptosis in microglia. Our time-lapse observations showed that lipopolysaccharide (LPS) stimulation induced rapid death in primary cultures of rat microglia, while a portion of the microglia escaped from death and survived for much longer than 2 days, in which time, all of the control cells had died. However, it remains unclear how the LPS-stimulated microglia subpopulation could continue to survive in the absence of any supplied growth factors.

The Subcellular Dynamics of the Gs-Linked Receptor GPR3 Contribute to the Local Activation of PKA in Cerebellar Granular Neurons.

G-protein-coupled receptor (GPR) 3 is a member of the GPR family that constitutively activates adenylate cyclase. We have reported that the expression of GPR3 in cerebellar granular neurons (CGNs) contributes to neurite outgrowth and modulates neuronal proliferation and survival. To further identify its role, we have analyzed the precise distribution and local functions of GPR3 in neurons.

Identification and characterization of PKCγ, a kinase associated with SCA14, as an amyloidogenic protein.

Amyloid assemblies are associated with a wide range of human disorders, including Alzheimer's and Parkinson's diseases. Here, we identify protein kinase C (PKC) γ, a serine/threonine kinase mutated in the neurodegenerative disease spinocerebellar ataxia type 14 (SCA14), as a novel amyloidogenic protein with no previously characterized amyloid-prone domains. We found that overexpression of PKCγ in cultured cells, as well as in vitro incubation of PKCγ without heat or chemical denaturants, causes amyloid-like fibril formation of this protein.

The role of Pak-interacting exchange factor-β phosphorylation at serines 340 and 583 by PKCγ in dopamine release.

Protein kinase C (PKC) has been implicated in the control of neurotransmitter release. The AS/AGU rat, which has a nonsense mutation in PKCγ, shows symptoms of parkinsonian syndrome, including dopamine release impairments in the striatum. Here, we found that the AS/AGU rat is PKCγ-knock-out (KO) and that PKCγ-KO mice showed parkinsonian syndrome.

Negative charges in the flexible N-terminal domain of Rho GDP-dissociation inhibitors (RhoGDIs) regulate the targeting of the RhoGDI-Rac1 complex to membranes.

In its resting state, Rho GDP-dissociation inhibitor (RhoGDI) α forms a soluble cytoplasmic heterodimer with the GDP-bound form of Rac. Upon stimulation, the dissociation of RhoGDIα from the RhoGDIα-Rac complex is a mandatory step for Rac activation; however, this mechanism is poorly understood. In this study, we examined how the cytoplasm/membrane cycles of the RhoGDI-Rac complex are regulated, as well as where RhoGDI dissociates from the RhoGDI-Rac complex, during FcγR-mediated phagocytosis.

Anti-Hu-associated paraneoplastic encephalomyelitis with esophageal small cell carcinoma.

A 63-year-old woman had anti-Hu-associated paraneoplastic encephalomyelitis (anti-Hu syndrome) caused by esophageal small cell carcinoma (SCC). The patient developed bilateral limbic encephalitis, followed by myelitis, brain stem encephalitis, and autonomic failure. Extensive examination demonstrated SCC of the abdominal lymph nodes that was retrospectively diagnosed as metastasis of esophageal SCC on autopsy.

Measurement of platelet-derived microparticle levels using an enzyme-linked immunosorbent assay in polymyositis and dermatomyositis patients.

Platelet-derived microparticle (PDMP) levels were measured using an enzyme-linked immunosorbent assay (ELISA) to elucidate the role of platelet activation in patients with polymyositis or dermatomyositis (PM/DM). PDMP levels in active PM/DM patients (median 13.3 U/ml, interquartile range 9.

[Case of LGMD2A (calpainopathy) clinically presenting as Miyoshi distal myopathy].

We reported a 23-year-old woman with distal myopathy and highly elevated serum creatine kinase (CK) caused by calpainopathy. Although muscle weakness was not evident, a muscle CT scan revealed replacement by adipose tissue in the medial head of the gastrocnemius. The gluteus maximus and biceps femoris were also affected to a lesser degree, but the lateral head of the gastrocnemius was preserved.

Measurement of platelet-derived microparticle levels in the chronic phase of cerebral infarction using an enzyme-linked immunosorbent assay.

Assessment of platelet function is a critical component of the treatment and secondary prevention of cerebral infarction, and measurement of platelet-derived microparticle (PDMP) levels using flow cytometry may be a good indicator of platelet function. However, the flow cytometric analysis is not feasible in a variety of clinical situations. The goal of the present study was to measure PDMP levels using an enzyme-linked immunosorbent assay (ELISA) in chronic cerebral infarction patients and to determine the utility of PDMP level measurement for the monitoring of the effect of cilostazol and aspirin.

[Case of suspected multiple sclerosis with transcallosal lesions involving the upper surface of the corpus callosum].

A 26-year-old woman noticed gradually progressive, right lower leg weakness over a 1.5-month period. Neurological examination revealed right hemiparesis with slightly increased deep tendon reflexes, Babinski's sign on the right side, loss of position sense in the right leg, and slight loss of superficial sensation in the right toes.

[Intermittent intravenous immunoglobulin infusion prevented relapses in patients with remission-exacerbation type chronic inflammatory demyelinating polyradiculoneuropathy].

The intravenous immunoglobulin infusion therapy (IVIg) has recently acquired an important role in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Some patients, however, require repetitive infusions to maintain the improvement. We planned a one-day therapy with 0.

[Long-term treatment of diabetes mellitus in myotonic dystrophy with pioglitazone].

We report beneficial effects of pioglitazone on insulin resistance in diabetes mellitus accompanied with myotonic dystrophy (DM1). We studied eight DM1 patients with diabetes mellitus aged 32 to 60 (mean age 52.1 +/- 8.