Microtubule Poisons

Dustin, Pierre

doi:10.1007/978-3-642-96436-7_7

Cited by 12 publications

(11 citation statements)

References 188 publications

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“…The difference in diameter of the filaments described by the present authors might be explained by a difference in processing method. The filaments seem identical with the intermediate filaments described in mesenchymal cells of the mouse (Dustin, 1978). Such filaments are also present in a number of cancer cells (Napolitano et al, 1964;Cardell and Knighton, 1966;Tumilowicz and Sarker, 1972;Lazarides, 1980) and mostly Figs.…”

Section: Discussionsupporting

confidence: 75%

Leydig cell development of pig testis in the early fetal period: An ultrastructural study

Vorstenbosch¹,

Colenbrander²,

Wensing³

1982

Am. J. Anat.

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Leydig cell development in the pig testis occurs in three periods (an early fetal, the perinatal period, and the period from puberty onward). The earliest of these periods was investigated ultrastructurally. The early fetal period starts immediately after gonadal differentiation, approximately 27 days postcoitum (p.c.), and finishes at about 60 days postcoitum. Dates of observation were 35, 52, and 62 days p.c. At 42 days p.c. some animals were decapitated. Leydig cells at 35 days p.c. are characterized by an oval nucleus, vesicular or branched tubular smooth endoplasmic reticulum (SER), and a small quantity of rough endoplasmic reticulum (RER). The RER has two forms: a short and a long profile. The latter is closely coupled with mitochondria. The mitochondria mostly have tubular cristae. From 52 days p.c. onward the degree of coupling lessens, and it vanishes at 62 days p.c. At 52 and 62 days p.c. a very large amount of 10 nm filaments and a slight decrease in SER can be observed. The SER now has a branched tubular form, and the presence of polygonal dense bodies is also characteristic. Decapitation does not disturb normal development of the Leydig cells in the observation period. No obvious differences from controls can be observed.

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Section: Discussionsupporting

confidence: 75%

Leydig cell development of pig testis in the early fetal period: An ultrastructural study

Vorstenbosch¹,

Colenbrander²,

Wensing³

1982

Am. J. Anat.

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“…Colchicine retards translocation of secretory proteins such as collagen (40), probably by the association of colchicine with the microtubular apparatus (41). Cytochalasin B also inhibits translocation of collagen (40) but does so by disorganizing microfilaments (42).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the production of secretory proteins: Intracellular degradation of newly synthesized “defective” collagen

Berg

Schwartz

Crystal

1980

Proc. Natl. Acad. Sci. U.S.A.

159

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Confluent cultures of human fetal lung fibroblasts degrade approximately 10% of their newly synthesized collagen within the cell prior to secretion. This basal level of intracellular degradation could not be inhibited by colchicine or cytochalasin B, inhibitors of microtubular and microfilament function, respectively, or by N -tosyl-L-lysine chloromethyl ketone, chloroquine, or NH4C1, inhibitors of Iysosomal enzymes.In contrast, cells in early logarithmic growth degrade approximately 30% of their newly synthesized collagen. This enhanced degradation of collagen in rapidly growing cells could be suppressed by inhibitors of lysosomal proteases and partially inhibited by disrupters of microtubular and microfilament function. A significant prootion of the collagen synthesized by these cultures contained prolyl residues that were incompletely hydroxylated. Because such collagen is "defective" (i.e., not capable of assuming a triple helical conformation), the results suggest that enhanced intracellular degradation may be a mechanism by which cells control the quality of collagen they produce. To test this hypothesis, confluent cells were incubated with the proline analog cis4hydroxyproline; such cells demonstrated en anced collagen degradation that could be inhibited by agents that interfere with lysosomal, microtubular, or microfilament function. Because collagen containing cis4 hydroxyproline cannot form a perfect triple helix, the data are consistent with the concept that defective collagen is recognized by cells and degraded prior to secretion. Thus, the proportion of newly synthesized collagen that undergoes intracellular degradation seems to be modulated, in part, by the conformation of the collagen molecule. Intracellular proteolysis may represent a means by which collagen-producing cells regulate the quality and quantity of collagen available for extracellular function. Although the exact mechanism of intracellular collagen degradation is unknown, the data presented here are consistent with a role for lysosomal proteases in this process. The normal collagen molecule is a triple helical, rod-like structure. Inherent in this structure is the property to polymerize into extracellular fibers that play a major role in defining organ structure and function (1-4). The ability of collagen to form fibers is dependent on its triple helical conformation. To form this helix, each collagen polypeptide chain must have a specific primary sequence, the most important aspect of which is a repetitive Gly-X-Y triplet; approximately 30% of the X residues are proline and 30% of the Y residues are trans-4-hydroxyproline (1)(2)(3)(4)(5). Several studies have demonstrated that, if a sufficient number of Y position residues are not filled with hydroxyproline, the resulting collagen molecule is "defective"-i.e., it cannot form a perfect triple helical structure at body temperature (5). Such defective collagen molecules will not polymerize into normal collagen fibers and thus cannot serve their function in the extracellular mat...

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“…1) and its congeners can be conveniently described in terms of the three rings of the molecule, the A ring or trimethoxybenzene moiety, the seven-membered B ring, and the methoxytropone moiety or C ring. Substantial evidence has accumulated that the colchicine-binding site of tubulin, through which most of the desired drug effect presumably must operate, contains a domain that recognizes the A ring and a second domain that recognizes the C ring (1)(2)(3). This was first concluded from the finding that podophyllotoxin competed for colchicine, presumably through the mutual trimethoxybenzene moiety (4).…”

mentioning

confidence: 99%

B ring regulation of colchicine binding kinetics and fluorescence.

Bhattacharyya

Howard

Maity

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Communicated by J. E. Rall, November 22, 1985 ABSTRACT Several properties of the colchicine-tubulin interaction such as association rate, reversibility, and the promotion of drug fluorescence have been related to the B ring of colchicine. The B ring itself retards the binding rate, and substitution at C-7 leads to further binding rate decreases that appear to be related to both substituent bulk and the presence of a N-acyl group. Thus, the decreasing order of binding rates is 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone > deacetamidocolchicine > deacetylcolchicine a colcemid > colchicine > N-benzoyldeacetylcolchicine, etc. The apparent irreversibility of the binding seems more closely related to the presence of an N-acyl group rather than the bulk of the substituent at C-7. Substitution at C-7 also affects the tropolone fluorophore. Thus, amines (deacetylcholchicine, colcemid, or N-methylcolcemid) fluoresce poorly in the presence of tubulin, whereas substitution of the amino group with an acyl group enhances fluorescence. The presence of an N-acyl group at C-7 is essential for enhanced fluorescence. We conclude that, in addition to A-and the C-ring portion ofthe molecule, the B ring of colchicine is a third determinant recognized by the binding site on tubulin.

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Microtubule Poisons

Cited by 12 publications

References 188 publications

Leydig cell development of pig testis in the early fetal period: An ultrastructural study

Leydig cell development of pig testis in the early fetal period: An ultrastructural study

Regulation of the production of secretory proteins: Intracellular degradation of newly synthesized “defective” collagen

B ring regulation of colchicine binding kinetics and fluorescence.

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