Carla Perrone Capano

Professor of Physiology
Vice-director of the CIRN

Name Carla
Surname Perrone Capano
Institution University of Naples – Federico II
Address Institute of Genetics and Biophysics, "Adriano Buzzati Traverso", CNR, 80131 Naples, Italy
Carla Perrone Capano


  • Regionalized neurofilament accumulation and motoneuron degeneration are linked phenotypes in wobbler neuromuscular disease.

    Publication Date: 01/08/2001 on Neurobiology of disease
    by Pernas-Alonso R, Perrone-Capano C, Volpicelli F, di Porzio U
    DOI: 10.1006/nbdi.2001.0403

    Abnormal neurofilament aggregates are pathological hall-mark of most neurodegenerative diseases, although their pathogenic role remains unclear. Increased expression of medium neurofilament (NFM) is an early molecular marker of wobbler mouse, an animal model of motoneuron disease. In the wr/wr, a vacuolar neuronal degeneration (VND) starts at 15 days postnatally, selectively in cervical spinal cord and brain stem motoneurons. Here we show that nfm gene hyperexpression is restricted to the aforementioned motoneurons and is specific for wr mutation. NF proteins accumulate in wr/wr before VND. wr/+ mice, which are asymptomatic, show intermediate NF accumulation between wr/wr and +/+ littermates, suggesting a gene dosage dependence of the wobbler pathology. Altogether our data indicate that NF hyperexpression and regionalized motoneuron degeneration are linked to the wr mutation, although with a still unknown relationship to the mutant gene activity.

  • Neurofilament homeostasis and motoneurone degeneration.

    Publication Date: 01/01/2001 on BioEssays : news and reviews in molecular, cellular and developmental biology
    by Perrone Capano C, Pernas-Alonso R, di Porzio U
    DOI: 10.1002/1521-1878(200101)23:1<24::AID-BIES1004>3.0.CO;2-H

    Neurofilament disorganisation is a hallmark of various neurodegenerative diseases. We review here current knowledge of neurofilament structure, gene expression and function. Neurofilament involvement in motoneurone neurological diseases is discussed in view of recent data from transgenic and spontaneous mouse mutants. In the mammalian neurone, the three neurofilament subunits are assembled into intermediate filaments as obligate heteropolymers. The subunits are expressed differentially during development and adult life according to the cell type and its physiological state. In addition to the well-established role of neurofilaments in the control of axonal calibre, there is increasing evidence that neurofilaments can interact with other cytoskeletal components and can modulate the axoplasmic flow. Although the extent to which neurofilament abnormalities contribute to the pathogenesis in human diseases remains unknown, emerging evidence suggests that disorganised neurofilaments can provoke degeneration and death of neurones. BioEssays 23:24-33, 2001.

  • Genetic and epigenetic control of midbrain dopaminergic neuron development.

    Publication Date: 01/01/2000 on The International journal of developmental biology
    by Perrone-Capano C, Di Porzio U

    The relatively few dopaminergic (DA) neurons in the mammalian brain regulate many important neural functions, including motor integration, neuroendocrine hormone release, cognition, emotive behaviors and reward. A number of laboratories, including ours, have contributed to unravel the mechanisms of DA phenotype induction and maturation and elucidated the role of epigenetic factors involved in specification, development and maintenance of midbrain dopaminergic functions. DA progenitors are first "committed" to give rise to DA neurons by the action of two secreted factors, Sonic hedgehog and fibroblast growth factor 8 (FGF8). Subsequently, the function of selectively activated transcription factors, Nurr1 and Ptx3, is required for the DA final determination. Further development of DA neurotransmission requires specific interactions with the developing target striatal cells, which modulate key DA functions, namely synthesis and uptake of the neurotransmitter. Committed and determined DA neurons express the key genes involved in DA neurotransmission at different times in development. In rodents, synthesis and intracellular accumulation of DA is achieved shortly after expression of Nurr1, while the onset of high affinity uptake, responsible for ending the neurotransmission, takes place after a few days. Cell contacts between the presynaptic DA neurons and target striatal neurons are apparently necessary for the fine modulation of DA function, in vivo and in vitro. Strikingly, the in situ maturation and phenotypic specialization of DA neurons grafted into the adult striatum/caudate-putamen parallels the normal development of committed fetal dopamine neurons during neurogenesis. The correct matching between the right presynaptic and postsynaptic neurons is required also for grafted DA cells.

  • Epigenetic cues in midbrain dopaminergic neuron development.

    Publication Date: 01/01/2000 on Neuroscience and biobehavioral reviews
    by Perrone-Capano C, Da Pozzo P, di Porzio U

    Midbrain dopaminergic (DA) neurons subserve complex and varied neural functions in vertebrate CNS. Their progenitors give rise to DA neurons by the action of two extracellular inducers, Sonic Hedgehog and FGF8. After this first commitment, the function of selectively activated transcription factors, like the orphan steroid nuclear receptor Nurr1, is required for DA final determination. Subsequently, DA function is selectively modulated by specific interaction with the developing striatal target tissue. Committed and determined DA neurons express the key genes involved in DA neurotransmission at different times in development. Synthesis and intracellular accumulation of DA is achieved shortly after expression of Nurr1, while high affinity uptake, responsible for ending the neurotransmission, takes place after a few days. Cell contacts between the presynaptic DA neurons and target striatal neurons are apparently necessary for the fine modulation of DA function, in vivo and in vitro.

  • Ribosomal RNAs synthesized by isolated squid nerves and ganglia differ from native ribosomal RNAs.

    Publication Date: 01/03/1999 on Journal of neurochemistry
    by Perrone-Capano C, Crispino M, Menichini E, Kaplan BB, Giuditta A

    The large rRNA of the squid comprises two chains that may be dissociated by heating at 65 degrees C. A single chain constitutes the small rRNA. Surprisingly, the RNAs synthesized by dissected squid fin nerves and stellate nerves and ganglia differed in size from native rRNAs and did not manifest thermal instability. Nonetheless, they resembled native rRNAs in relative abundance, subcellular distribution, lack of poly(A), and metabolic stability. In addition, newly synthesized RNA was localized in nerve and glial cells, as shown by autoradiographic analysis, and was assembled into 80S ribosomes, which supported the synthesis of neuron-specific neurofilament proteins. Following incubation of nerves and ganglia for >10 h, native rRNAs started to disappear, while two major newly synthesized RNAs progressively accumulated. As a result, after 20 h, native rRNAs were substituted by the two novel RNAs. With use of 32P-cDNA synthesized from the latter RNAs as a probe, the novel RNAs demonstrated a considerable degree of homology with native rRNA in northern analysis. Taken together, the data suggest that in dissected squid nerves and ganglia, the synthesis of native rRNAs is gradually terminated while two novel rRNAs are being synthesized, presumably as a correlate of reactive gliosis and/or neuronal degeneration/regeneration.

  • Dystrophin localization and gene expression in the developing nervous system of the chick.

    Publication Date: 01/01/1998 on Journal of neuroscience research
    by Perrone-Capano C, Crispino M, Oteri G, Tata AM, Vignoli AL, Poiana G
    DOI: 10.1002/(SICI)1097-4547(19980101)51:1<109::AID-JNR12>3.0.CO;2-6

    The presence and distribution of dystrophin was studied in selected areas of the chick embryo nervous system and in primary cultures. Dystrophin was examined at the protein level by immunocytochemistry and at the transcriptional level by a semiquantitative reverse transcriptase-polymerase chain reaction analysis. Immunofluorescence staining shows that dystrophin is present early during embryogenesis in dorsal root ganglia, spinal cord, and ciliary ganglia and colocalizes with neurofilament subunits. Cultured dorsal root ganglion, spinal cord, and ciliary ganglion neurons show immunoreactivity for dystrophin, both in cell bodies and along fibers. Dystrophin mRNA level in ciliary and dorsal root ganglia is higher than in spinal cord throughout development and shows a tissue-specific pattern of expression. In primary cultures of dorsal root ganglia and ciliary ganglia, dystrophin mRNA level increases with time in vitro. However, in spinal cord cultures, dystrophin mRNA drastically decreases with time in vitro, but it is significantly increased when embryonic muscle extract is added to the cultures. Our results show that dystrophin is present in neurons from different areas of embryonic chick nervous system and that its mRNA level is developmentally regulated both in vivo and in vitro.

  • Dopamine transporter gene expression in rat mesencephalic dopaminergic neurons is increased by direct interaction with target striatal cells in vitro.

    Publication Date: 01/07/1996 on Brain research. Molecular brain research
    by Perrone-Capano C, Tino A, Amadoro G, Pernas-Alonso R, di Porzio U

    By using a semi-quantitative reverse transcriptase-PCR assay (RT-PCR) we have analyzed dopamine transporter (DAT), tyrosine hydroxylase (TH) and synaptic vesicle monoamine transporter (VMAT2) gene expression in rat mesencephalic (MES) primary cultures. Consistent with previous data obtained during rat MES ontogeny, the onset of DAT transcription in vitro is delayed in embryonic day (E)13, but not in E16, MES neurons when compared to that of TH and VMAT2. In co-culture, the addition of target striatal cells (STR) to E13 MES selectively increases DAT mRNA level in DA neurons during the first 3 days in vitro; cortical cells are ineffective. On the contrary, DAT gene does not appear up-regulated in E16 MES co-cultured with target STR cells, indicating that MES DA neurons respond to STR stimulation only at defined developmental stages. Up-regulation of DAT mRNA level by STR in E13 MES seems to require direct cell interactions since target cells do not exert their effect on DAT transcription when are separated from MES cells by a porous barrier, which only allows diffusion of soluble molecules. Thus maturation of DA neurotransmission in vitro appears to follow a developmental program which can be specifically modulated by their target STR cells.

  • Target cells modulate dopamine transporter gene expression during brain development.

    Publication Date: 09/05/1994 on Neuroreport
    by Perrone-Capano C, Tino A, di Porzio U

    We have analysed the expression of the dopamine transporter (DAT) gene and compared it with that of tyrosine hydroxylase, neuronal GABA transporter and synaptic vesicle monoamine transporter genes during pre- and post-natal development of rat mesencephalic dopaminergic (DA) neurones. Our results show that DAT transcripts are not detectable until embryonic day (E) 15, whilst those of the other genes analysed are already present at E12. In vitro, the level of DAT gene transcription in mesencephalic E13 DA neurones is increased in coculture with target striatal cells. Thus striatal targets cells regulate, at the transcriptional level, a key step of dopaminergic neurotransmission during DA neurone development.

  • Protein synthesis in a synaptosomal fraction from squid brain.

    Publication Date: 01/08/1993 on Molecular and cellular neurosciences
    by Crispino M, Castigli E, Perrone Capano C, Martin R, Menichini E, Kaplan BB, Giuditta A
    DOI: 10.1006/mcne.1993.1046

    A synaptosomal fraction from squid brain containing a large proportion of well-presarved nerve terminals displays a high rate of [(35)S]methionine incorporation into protein. The reaction is dependent on time and protein concentration, is strongly inhibited by hypo-osmotic shock and cycloheximide, and is not affected by RNase. Chloramphenicol, an inhibitor of mitochondrial protein synthesis, partially inhibits the reaction. The ionic composition of the incubation medium markedly modulates the rate of [(35)S]methionine incorporation. Na(+) and K(+) ions are required for maximal activity, while complete inhibition is achieved by addition of the calcium ionophore A23187 and, to a substantial extent, by tetraethylammonium, ouabain, and high concentrations K(+). A thermostable inhibitor of synaptosomal protein synthesis is also present in the soluble fraction of squid brain. Using sucrose density gradient sedimentation procedures, cytoplasmic polysomes associated with nascent radiolabeled peptide chains have been identified in the synaptosomal preparation. Newly synthesized synaptosomal proteins are largely associated with a readily sedimented particulate fraction and may be resolved by gel electrophoresis into more than 30 discrete bands ranging in size from about 14 to 200 kDa. The electrophoretic pattern of the newly synthesized synaptosomal proteins is significantly different from the corresponding patterns displayed by the giant axon's axoplasm and by glial and nerve cell bodies (in the stellate nerve and ganglion, respectively). On the whole, these observations suggest that the nerve endings from squid brain are capable of protein synthesis.

  • Active polysomes in the axoplasm of the squid giant axon.

    Publication Date: 01/01/1991 on Journal of neuroscience research
    by Giuditta A, Menichini E, Perrone Capano C, Langella M, Martin R, Castigli E, Kaplan BB
    DOI: 10.1002/jnr.490280103

    Axons and axon terminals are widely believed to lack the capacity to synthesize proteins, relying instead on the delivery of proteins made in the perikaryon. In agreement with this view, axoplasmic proteins synthesized by the isolated giant axon of the squid are believed to derive entirely from periaxonal glial cells. However, squid axoplasm is known to contain the requisite components of an extra-mitochondrial protein synthetic system, including protein factors, tRNAs, rRNAs, and a heterogeneous family of mRNAs. Hence, the giant axon could, in principle, maintain an endogenous protein synthetic capacity. Here, we report that the squid giant axon also contains active polysomes and mRNA, which hybridizes to a riboprobe encoding murine neurofilament protein. Taken together, these findings provide direct evidence that proteins (including the putative neuron-specific neurofilament protein) are also synthesized de novo in the axonal compartment.