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In cathepsin D-deficient (CD-/-) and cathepsins B and L double-deficient (CB-/-CL-/-) mice, abnormal vacuolar structures accumulate in neurons of the brains. Many of these structures resemble autophagosomes in which part of the cytoplasm is retained but their precise nature and biogenesis remain unknown. We show here how autophagy contributes to the(More)
The phosphorylated carboxyl-terminal "tail" domains of the neurofilament (NF) subunits, NF heavy (NF-H) and NF medium (NF-M) subunits, have been proposed to regulate axon radial growth, neurofilament spacing, and neurofilament transport rate, but direct in vivo evidence is lacking. Because deletion of the tail domain of NF-H did not alter these axonal(More)
Neurofilaments are essential for acquisition of normal axonal calibers. Several lines of evidence have suggested that neurofilament-dependent structuring of axoplasm arises through an "outside-in" signaling cascade originating from myelinating cells. Implicated as targets in this cascade are the highly phosphorylated KSP domains of neurofilament subunits(More)
The COOH-terminal tail of mammalian neurofilament heavy subunit (NF-H), the largest neurofilament subunit, contains 44-51 lysine-serine-proline repeats that are nearly stoichiometrically phosphorylated after assembly into neurofilaments in axons. Phosphorylation of these repeats has been implicated in promotion of radial growth of axons, control of nearest(More)
Neurofilament medium (NF-M) is essential for the acquisition of normal axonal caliber in response to a myelin-dependent "outside-in" trigger for radial axonal growth. Removal of the tail domain and lysine-serine-proline (KSP) repeats of NF-M, but not neurofilament heavy, produced axons with impaired radial growth and reduced conduction velocities. These(More)
To find out what causes differences in phosphorylation states in neurofilaments (NF), we selected two types of dendrite, one provided with very few NFs (Purkinje cell) and the other with relatively many (anterior horn cell). We examined these with four monoclonal antibodies selected by the Western blot analysis, two (NE14 and SMI31) recognizing only(More)
We previously reported that myelin-associated oligodendrocytic basic protein (MOBP) was abundantly expressed in the central nervous system (CNS) myelin, and shared several characteristics with myelin basic protein (MBP). In particular, a cluster of positively charged amino acids was considered to facilitate compaction of the cytoplasmic face of the myelin(More)
1. In the eye, different substances and ions including potassium (K+) are transported between neural retina and choroid via the subretinal space. Inwardly rectifying K+ channels (Kir) on the apical membrane of retinal pigment epithelial (RPE) cells are thought to play an essential role in K+ transport in the subretinal space. 2. Single-channel recordings(More)
Cytoplasmic architecture of axon terminals in rat central nervous tissue was examined by quick-freeze deep-etch method to determine how synaptic vesicles and their associated cytoplasmic environment are organized in the terminal and to know how these structures participate in the mechanism for neurotransmitter release. The axoplasm is divisible into two(More)
With dendritic neurofilaments (NFs) and NF reassembly experiments, the phosphorylation of NF-H was found related to development of crossbridges, resulting in alignment of core filaments. When treated with aluminum chloride, rabbits died acutely with tetanic spasm in which NFs were accumulated in neuronal perikarya and proximal axons. Compared with axonal(More)