A disintegrin and metalloprotease 21 (ADAM21) is associated with neurogenesis and axonal growth in developing and adult rodent CNS

Abstract

We have reported that alpha6beta1 integrin regulates the directed migration of neuroblasts from the adult rodent subventricular zone (SVZ) through the rostral migratory stream (RMS). ADAM (a disintegrin and metalloprotease) proteins bind integrins. Here, we show that ADAM21, but not ADAM2, -3, -9, -10, -12, -15, or -17, is expressed in adult rats and mice by ependyma and SVZ cells with long basal processes, and in radial glia at early postnatal times. ADAM21-positive processes projected into the RMS, contacted blood vessels, and were present within the RMS intermingled with neuroblasts up to where neuroblasts start their radial migration and differentiation in the olfactory bulb. Tissue inhibitors of metalloproteases (TIMPs) 1, 2, and 3 are present in the ependymal layer but not in the SVZ and RMS. Thus, ADAM21 could regulate neurogenesis and guide neuroblast migration through cleavage-dependent activation of proteins and integrin binding. ADAM21 is also present in growing axonal tracts during postnatal development and in growing primary olfactory axons in adults. In the olfactory nerve layer, ADAM21 often, but not always, colocalizes with OMP, a marker of mature olfactory neurons, but is not colocalized with the immature marker betaIII-tubulin. This suggests that ADAM21 is involved in the final axonal outgrowth phase and/or synapse formation. TIMP3 is present in periglomerular neurons, where it could restrict ADAM21-mediated axonal growth to the glomeruli. ADAM21's unique disintegrin and metalloprotease sequences and its restricted expression suggest that it might be a good target for influencing neurogenesis and neuronal plasticity.

Role of Megakaryoblastic Acute Leukemia-1 in ERK1/2-Dependent Stimulation of Serum Response Factor-Driven Transcription by BDNF or Increased Synaptic Activity

“…All animals were treated in accordance with the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the University of Louisville Guidelines for the Care and Use of Laboratory Animals. Anesthetized animals were perfused transcardially, and free-floating 30-m-thick coronal brain sections were prepared after postfixation (Yang et al, 2005). For staining, sections were washed in Tris-buffered saline (TBS; 0.05 mM Tris and 0.9% NaCl, pH 8.0), the endogenous peroxidase was quenched for 5 min (10% methanol and 1% H 2 O 2 in TBS), and the cell membrane was permeabilized (15 min in 0.2% Triton X-100 in TBS).…”

Targeting MMPs in Acute and Chronic Neurological Conditions

“…A member of a related protease family, ADAM21, has also been implicated in events occurring at the rostral migratory stream, such as axonal outgrowth. 18 Mice deficient in particular MMPs have highlighted the importance of MMPs in CNS development. MMP-14 null mice have smaller craniums than wild type controls, 19 and MMP-9 null mice have abnormal development of cerebellar granule neurons 20 and cortex.…”

TCR variable gene involvement in chromosome inversion between 14q11 and 14q24 in adult T-cell leukemia

“…ADAM21-L was found to possess 2 transmembrane domains with no signal sequence at the N-terminal end, compared to 3 transmembrane domains with a signal sequence in ADAM21. This difference in the N-terminal structure explains the observation that ADAM21-L is observed in the nucleus as well as the cytoplasm, while the ADAM21 protein is localized to the cellular membrane (Yang et al 2005). We studied expression of the ADAM21-L gene using ATL-derived cell lines (Fig.…”