Abstract
Tau is a cytoskeletal protein that is expressed mainly in neurons and is involved in several cellular processes, such as microtubule stabilization, axonal maintenance, and transport. Altered tau metabolism is related to different tauopathies being the most important Alzheimer’s disease where aberrant hyperphosphorylated and aggregated tau is found in the central nervous system. Here, we have analyzed that function in kidney by using tau knockout mice generated by integrating GFP-encoding cDNA into exon 1 of MAPT (here referred to as TauGFP/GFP). IVIS Lumina from PerkinElmer demonstrated GFP expression in the kidney. We then demonstrated by qPCR that the main tau isoform in the kidney is Tau4R. The GFP reporter allowed us to demonstrate that tau is found in the glomeruli of the renal cortex, and specifically in podocytes. This was further confirmed by immunohistochemistry. TauGFP/GFP mice present a podocyte cytoskeleton more dynamic as they contain higher levels of detyrosinated tubulin than wild-type mice. In addition, transmission electron microscopy studies demonstrated glomerular damage with a decrease in urinary creatinine. Our results prove that tau has an important role in kidney metabolism under normal physiological conditions.
Highlights
Tau is a microtubule-associated protein that plays a critical role in the pathogenesis of several disorders in the nervous system collectively known as tauopathies [1,2,3]
We investigated tau promoter expression using GFP fluorescent imaging with the IVIS Lumina II system, a rapid ex vivo whole-organ imaging system for determining GFP expression, in T auGFP/GFP mice (animals with two GFP copies that are knockout mice for the microtubule-associated protein tau (MAPT) gene due to insertion of the transgene GFP)
The presence of tau was further confirmed by immunoblot and we found a main band of apparent molecular weight of 52 kDa (Fig. 3C)
Summary
Tau is a microtubule-associated protein that plays a critical role in the pathogenesis of several disorders in the nervous system collectively known as tauopathies [1,2,3]. Alzheimer’s disease is the most prevalent tauopathy and the main cause of dementia among older adults. In this disease, intracellular tau protein forms filamentous structures of aggregated protein which are associated with neuronal death. Tau in polymerized or monomeric form is released into the extracellular space through physiological and pathological mechanisms and extracellular tau can be toxic for neighboring cells [4]. This effect may contribute to the progression of a number of neurodegenerative diseases [4, 5]. Its presence has been demonstrated in several cell types and tissues, including pancreatic acinar cells [20], denervated rat muscles [21], monocytes [22], testicular spermatid [23], HeLa cells as well as in non-transformed fibroblasts and lymphocytes [24, 25], skin fibroblasts [26], hepatoma cell line [25], and human prostate cancer cell [25,
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