Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary neuropathies are classified into several subtypes according to clinical, electrophysiologic and pathologic findings. Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1). In the primary peripheral axonal neuropathies(CMT2), at least 8 genes have been associated with these disorders; the neurofilament light chain gene(NEFL), the kinesin 1B gene(KIF1B), the gigaxonin gene(GAN1), Lamin A/C(LMNA) and tyrosyl-DNA phosphodiesterase 1(TDP1). In addition, some mutations in GJB1, MPZ and GDAP1 also present with clinical and electrophysiologic findings of CMT2. Mutation of NEFL or KIF1B cause dominantly inherited axonal neuropathies, whereas mutation of GJB1 or MPZ can present as genocopies of dominant axonal neuropathies. In addition to the above diseases, we have reported a new type of NMSNP(MIM # *604484) characterized by proximal dominant neurogenic atrophy, obvious sensory nerve involvement and the gene locus on 3q13. Here, we summarize the genetic bases of hereditary neuropathies and attempt to highlight significant genotype-phenotype correlations.
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PMID:[Molecular mechanisms of hereditary neuropathy: genotype-phenotype correlation]. 1288 40

How membrane biosynthesis and homeostasis is achieved in myelinating glia is mostly unknown. We previously reported that loss of myotubularin-related protein 2 (MTMR2) provokes autosomal recessive demyelinating Charcot-Marie-Tooth type 4B1 neuropathy, characterized by excessive redundant myelin, also known as myelin outfoldings. We generated a Mtmr2-null mouse that models the human neuropathy. We also found that, in Schwann cells, Mtmr2 interacts with Discs large 1 (Dlg1), a scaffold involved in polarized trafficking and membrane addition, whose localization in Mtmr2-null nerves is altered. We here report that, in Schwann cells, Dlg1 also interacts with kinesin 13B (kif13B) and Sec8, which are involved in vesicle transport and membrane tethering in polarized cells, respectively. Taking advantage of the Mtmr2-null mouse as a model of impaired membrane formation, we provide here the first evidence for a machinery that titrates membrane formation during myelination. We established Schwann cell/DRG neuron cocultures from Mtmr2-null mice, in which myelin outfoldings were reproduced and almost completely rescued by Mtmr2 replacement. By exploiting this in vitro model, we propose a mechanism whereby kif13B kinesin transports Dlg1 to sites of membrane remodeling where it coordinates a homeostatic control of myelination. The interaction of Dlg1 with the Sec8 exocyst component promotes membrane addition, whereas with Mtmr2, negatively regulates membrane formation. Myelin outfoldings thus arise as a consequence of the loss of negative control on the amount of membrane, which is produced during myelination.
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PMID:Dlg1, Sec8, and Mtmr2 regulate membrane homeostasis in Schwann cell myelination. 1958 93