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      Louis Reichardt: The long climb to science's summits

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      Journal: The Journal of Cell Biology
      Publisher: The Rockefeller University Press

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          Abstract

          From the highest mountains to biology's own Everest—the brain—Reichardt tackles the biggest challenges of climbing and biology.

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          Neurotransmitter synthesis and uptake by isolated sympathetic neurones in microcultures.

          L F Reichardt, P Patterson (1977)
          Assays of isolated single sympathetic neurones show that their transmitter functions can be either adrenergic or cholinergic depending on growth conditions. The data suggest that the number of transmitters made by most mature individual neurones is restricted.
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            Severe sensory and sympathetic deficits in mice lacking neurotrophin-3.

            L F Reichardt, Robert Backus, Malcolm K. Jones … (1994)
            During development, neurotrophins help shape the nervous system by regulating neuronal survival and differentiation. Neurotrophin-3 (refs 1-5) is the most abundant neurotrophin during early development. Neurons responsive to neurotrophin-3 in vitro include primary sensory, sympathetic, motor, enteric, locus coeruleus, hippocampal and cerebellar neurons (ref. 9 for example). Here we report that mice lacking neurotrophin-3 have severe deficits in sensory and sympathetic populations. These mice lack muscle spindles and show abnormal limb positions. In contrast, motor neurons, the enteric nervous system, and the major anatomical regions of the central nervous system seem to develop normally. Comparisons with mutants deficient in other neurotrophins or their receptors indicate that some neurons require more than one neurotrophin during embryogenesis and suggest that neurotrophin-3 functions by binding receptors in addition to its primary receptor trkC (ref. 16). In particular, neurotrophin-3 is essential for survival of sympathetic and sensory neurons that later become dependent on nerve growth factor or brain-derived neurotrophic factor.
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              Identification of a synaptic vesicle-specific membrane protein with a wide distribution in neuronal and neurosecretory tissue

              L.F. Reichardt, W.D. Matthew (1981)
              Two different monoclonal antibodies, characterized initially as binding synaptic terminal regions of rat brain, bind a 65,000-dalton protein, which is exposed on the outer surface of brain synaptic vesicles. Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals. The antibodies have been used successfully to purify synaptic vesicles from crude brain homogenates by immunoprecipitation onto the surface of polyacrylamide beads. The profiles of the structures precipitated by these beads are almost exclusively vesicular, confirming the vesicle-specificity of the antibodies. In SDS gels, the antibodies bind a single protein of 65,000 daltons. The two antibodies are not identical, but compete for binding sites on this protein. Immune competition experiments also demonstrate that the antigenic components on the 65,000-dalton protein are widely distributed in neuronal and neural secretory tissues. Detectable antigen is not found in uninnervated tissue--blood cells and extrajunctional muscle. Low levels are found in nonneural secretory tissues; it is not certain whether this reflects the presence of low amounts of the antigen on all the exocytotic vesicles in these tissues or whether the antigen is found only in neuronal fibers within these tissues. The molecular weight and at least two antigenic determinants of the 65,000-dalton protein are highly conserved throughout vertebrate phylogeny. The two antibodies recognize a 65,000-dalton protein present in shark, amphibia, birds, and mammals. The highly conserved nature of the determinants on this protein and their specific localization on secretory vesicles of many different types suggest that this protein may be essential for the normal function of neuronal secretory vesicles.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cell Biol
                Journal ID (hwp): jcb
                Title: The Journal of Cell Biology
                Publisher: The Rockefeller University Press
                ISSN (Print): 0021-9525
                ISSN (Electronic): 1540-8140
                Publication date (Print): 7 September 2009
                Volume: 186
                Issue: 5
                Pages: 634-635
                Author notes

                Text and Interview by Nicole LeBrasseur

                Article
                Publisher ID: 1865pi
                DOI: 10.1083/jcb.1865pi
                PMC ID: 2742192
                PubMed ID: 19736314
                SO-VID: 550282c6-edc2-405c-8337-0fb6ce69cc4b
                Copyright © © 2009 The Rockefeller University Press
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                Subject: People & Ideas

                ScienceOpen disciplines: Cell biology
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                ScienceOpen disciplines: Cell biology

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