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NIDA Proteomics Center
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Investigators
> Samuel Sathyanesan
Neurobiology of the Choroid
Plexus Proteome
Samuel Sathyanesan, Psychiatry,
Yale University The
choroid plexus (CP) is an important blood-cerebrospinal fluid barrier that is
chiefly recognized for its role in cerebrospinal fluid production. Recent
progress has shown that the CP expresses high levels of proteins that could be
involved in diverse brain functions, including transport of peripheral trophic
factors, amyloid –beta clearance, neurotransmitter metabolism, immune response
and obesity. Reduced CP function has been implicated in aging and Alzheimer’s
disease, while dysregulation of CSF transthyretin, a thyroid hormone distributor
protein whose CNS expression is exclusively in the CP, has been linked with
depression. The simple cellular composition of the CP and high levels of
serotonin receptor (5HT2C) expression render it an ideal system to elucidate
signaling networks. The emerging functions of the CP suggest that it is a
critical brain structure, that although understudied, holds much potential in
the context of neuropsychiatric disorders and their treatment. We have already
conducted a detailed genomics analysis of the CP transcriptome and identified
over 350 proteins using mass spectrometry techniques. The goals of this proposal
are 1) obtain a complete catalog of CP proteins; 2) develop methods to
accurately measure the trophic factors expressed in the CP and 3) characterize
the 5HT2C signaling network and phosphoproteome. These studies will be
accomplished by a combination of proteomics technologies, multidimensional
protein identification (MudPIT), multiple reaction monitoring (MRM/MS) and
immobilized metal affinity chromatography (IMAC/MS). It is expected that these
studies will provide major insight into the function of the blood-CSF barrier
and its contribution to overall brain function and homeostasis. |
