Action of Insulin on the Surface Morphology of Hepatocytes: Role of Phosphatidylinositol 3-kinase in Insulin-Induced Shape Change of Microvilli

Lange, Klaus; Brandt, Ursula; Gartzke, J.; Bergmann, J.

doi:10.1006/excr.1997.3894

Cited by 27 publications

(29 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Figure 11a-e, stimulation of Ca signaling in isolated rat hepatocytes by either vasopressin (B), thapsigargin (D), insulin (C), or ATP (E) always exhibits the same characteristic shape change of microvilli indicating the reorganization of the internal structure and loss of the microfilament diffusion barrier function (Lange et al, 1997(Lange et al, , 1998. Similar shape changes of microvilli could be found in response Ca signaling or Fig.…”

Section: Surface Morphology Of Ca Signalingmentioning

confidence: 66%

See 1 more Smart Citation

F‐actin‐based Ca signaling—a critical comparison with the current concept of Ca signaling

Lange¹,

Gartzke²

2006

Journal Cellular Physiology

View full text Add to dashboard Cite

A short comparative survey on the current idea of Ca signaling and the alternative concept of F-actin-based Ca signaling is given. The two hypotheses differ in one central aspect, the mechanism of Ca storage. The current theory rests on the assumption of Ca-accumulating endoplasmic/sarcoplasmic reticulum-derived vesicles equipped with an ATP-dependent Ca pump and IP3- or ryanodine-sensitive channel-receptors for Ca-release. The alternative hypothesis proceeds from the idea of Ca storage at the high-affinity binding sites of actin filaments. Cellular sites of F-actin-based Ca storage are microvilli and the submembrane cytoskeleton. Several specific features of Ca signaling such as store-channel coupling, quantal Ca release, spiking and oscillations, biphasic and "phasic" uptake kinetics, and Ca-induced Ca release (CICR), which are not adequately described by the current concept, are inherent properties of the F-actin system and its dynamic state of treadmilling.

show abstract

Section: Surface Morphology Of Ca Signalingmentioning

confidence: 66%

“…This concept is further strengthened by the discovery of specific morphological changes of the cell surface characteristic for the stimulated Ca-signaling pathway (Lange and Brandt, 1993a;Lange et al, 1997Lange et al, , 1998.…”

mentioning

confidence: 96%

F‐actin‐based Ca signaling—a critical comparison with the current concept of Ca signaling

Lange¹,

Gartzke²

2006

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Together, these observations support a structural and functional analogy in terms of insulin signaling between the caveola neck microdomains and plasma membrane microvilli, which both concentrate IRs. Noteworthy, we observed that insulin tends to relocate IRs from microvilli to the caveolar necks in 3T3-L1 cells, which might be because insulin can induce a shortening of microvilli and a preferential cytoskeleton polymerization at sites where IRs are mostly concentrated, thus partially relocating IRs from microvilli to caveolar necks (29,30).…”

Section: Discussionmentioning

confidence: 79%

The neck of caveolae is a distinct plasma membrane subdomain that concentrates insulin receptors in 3T3-L1 adipocytes

Foti

Porcheron

Fournier

et al. 2007

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

View full text Add to dashboard Cite

Insulin receptors (IRs) segregate on plasma membrane microvilli, but in cells devoid of microvilli, such as adipocytes, the localization of IRs is a matter of controversy. In the present study, we examined the distribution of IRs in the plasma membrane of 3T3-L1 adipocytes. Quantitative electron microscopy indicates that IRs are predominantly associated with the neck, but not the bulb, of caveolae. Caveola necks represent distinct microdomains of the plasma membrane. Indeed, as shown by freeze-fracture analysis, intramembrane particles are concentrated as necklaces around the craters of caveolae. In addition, subcellular fractionation suggests that the neck and the bulb of caveolae present a different resistance to detergent solubility. Finally, cytoskeletal components, including actin, are highly enriched in the membrane area underlying the neck part of caveolae. IRs coimmunoprecipitate with cytoskeletal components, and disruption of the actin cytoskeleton alters IRs expression, localization, and signaling, thus supporting the notion that caveola necks are involved in intracellular signaling by IRs. Together, these results suggest that cytoskeletal proteins anchor IRs to microdomains in the caveola necks of 3T3-L1 adipocytes. By homology with IR localization in other cell types, we suggest that the necks of caveolae may represent the counterpart of microvillar domains in cells poor in microvilli such as adipocytes and that they play an important role as signaling platforms.cytoskeleton ͉ electron microscopy

show abstract

“…An additional role in cell survival has been reported [14,15]. In hepatocytes, PtdIns 3-kinase contributes to the regulation of several biological functions, including EGF-induced and insulininduced mitogenesis [16], insulin-induced [17] and HGF-induced [18] morphogenesis, insulin-dependent inhibition of apolipoprotein B secretion [19] and autophagy [20]. PtdIns 3-kinase is a lipid (and serine) kinase capable of phosphorylating phosphatidylinositol (PtdIns), PtdIns(4)P and PtdIns(4,5)P 2 to produce PtdIns(3)P, PtdIns(3,4)P 2 and PtdIns(3,4,5)P 3 , respectively, although the major product in vivo is PtdIns(3,4,5)P 3 (reviewed in [21,22]).…”

mentioning

confidence: 99%

Involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3‐kinase in rat hepatocyte primary culture

Fujioka

2001

European Journal of Biochemistry

View full text Add to dashboard Cite

Short-term incubation of adult rat hepatocytes with epidermal growth factor (EGF) caused tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 when the cells had been submitted to primary culture from 1±18 h. Tyrosine-phosphorylated IRS-1 and IRS-2 bound to the regulatory subunit (p85) of phosphatidylinositol (PtdIns) 3-kinase, thereby activating the enzymic activity. Tyrosine phosphorylation of the IRSs and activation of PtdIns 3-kinase in 3 h cultured hepatocytes both proceeded similarly to the same actions of insulin; the activation was rapid and transient, with peak values at 15±30 s and with similar EC 50 s in the nm range in both cases. A possible involvement of insulin receptors in these insulin-like actions of EGF was excluded by the following three lines of evidence. Insulin caused tyrosine phosphorylation of the insulin receptor b-subunit but EGF did not. In contrast, the EGF receptor was phosphorylated by EGF, but the insulin receptor was not. The actions of EGF, but not those of insulin, were inhibited by AG1478, a selective inhibitor of EGF receptor tyrosine kinase. Cultured hepatocytes exposed to insulin or insulin-like growth factor-I (IGF-I) for a short period responded to the subsequent addition of EGF, whereas EGF-treated cells responded to insulin. The cells, however, displayed receptor desensitization under the same conditions, that is, no response was observed upon repeated addition of the same agonist, EGF, insulin or IGF-I. Thus, the EGF receptor-initiated signalling was mediated by PtdIns 3-kinase associated with tyrosine-phosphorylated IRSs in short-term cultured rat hepatocytes.Keywords: signal transduction; tyrosine kinase receptor; tyrosine phosphorylation.Membrane receptors having intrinsic protein tyrosine kinase activity are known to be responsible for promoting proliferation of hepatocytes [1] as well as many other types of cells [2]. If kept in a serum-free medium, DNA synthesis in hepatocytes occurs with the addition of growth factors, among which epidermal growth factor (EGF) is effective in vivo and in culture [3,4] as a result of its binding to typical tyrosine kinase related receptors. The EGF receptor (EGFR) is the prototype of the type I ErbB subfamily, which includes three additional members, ErbB-2/Neu, ErbB3 and ErbB4 [5]. All members of the ErbB subfamily have a domain that serves as a docking site for specific SH-2 domains, which are present in signalling proteins such as the p85 regulatory subunit of phosphatidylinositol (PtdIns) 3-kinase. EGF has been shown to activate PtdIns 3-kinase, although it does not bind directly to the EGFR but is instead activated via association with p120 cbl [6,7] or Gab1 [8], which are phosphorylated on tyrosine residues by the growth factor. PtdIns 3-kinase may also interact with heterodimers of other members of the EGFR family, such as ErbB3, in response to EGF [9,10].PtdIns 3-kinase plays important roles in a wide variety of biological responses to hormones, growth factors and cytokines [11]. The typical responses s...

show abstract

Action of Insulin on the Surface Morphology of Hepatocytes: Role of Phosphatidylinositol 3-kinase in Insulin-Induced Shape Change of Microvilli

Cited by 27 publications

References 49 publications

F‐actin‐based Ca signaling—a critical comparison with the current concept of Ca signaling

F‐actin‐based Ca signaling—a critical comparison with the current concept of Ca signaling

The neck of caveolae is a distinct plasma membrane subdomain that concentrates insulin receptors in 3T3-L1 adipocytes

Involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3‐kinase in rat hepatocyte primary culture

Contact Info

Product

Resources

About