Biomedical subjects

Biao He

Publications and source records attributed to Biao He.

At least 37 records · Page 2Linked to original sources

PubMed2004

Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma.

Secreted frizzled-related proteins (sFRPs) comprise a family of five secreted glycoproteins that antagonize Wnt signaling. Aberrant activation and upregulation of the Wnt pathway is a key feature of many cancers. Thus, role of sFRP as a negative regulator of Wnt signaling may have important implications in tumorigenesis, and its downregulation has been correlated with human cancers. Recently, we reported Wnt signaling and dishevelled (Dvl) overexpression in malignant pleural mesothelioma (MM). Here, we report significant transcriptional downregulation of the SFRP gene family in MM primary tissues and cell lines as well as several other cancer cell lines (breast, lung, glioma, and cervical) compared to normal cells. One or more SFRPs were downregulated in approximately 85% (18 of 21) of primary MM tumor specimens compared to normal pleural tissue. Eight of the nine cancer cell lines we examined showed silencing of the SFRP family. Methylation-specific PCR (MSP) analysis showed that SFRP1, SFRP4, and SFRP5 gene promoters are frequently methylated in MM primary tissue (>80%). Furthermore, transfection of the SFRP gene construct into MM cell lines lacking SFRP expression resulted in apoptosis and growth suppression. Our results suggest that methylation silencing of SFRPs may be one of the important mechanisms of aberrant Wnt signaling activation in MM.

Down-Regulation↗

PubMed2004

Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells.

In this report, we have demonstrated that Wnt-2 protein is overexpressed in freshly resected human non-small-cell lung cancer (NSCLC) tissues. We have also developed a monoclonal antibody against the N-terminus of human Wnt-2 protein. This monoclonal antibody induces apoptosis in human NSCLC cell lines that overexpress Wnt-2 protein. Incubation of this antibody with normal human airway cells lacking Wnt-2 expression does not induce apoptosis. Wnt-2 signaling blockade by the anti-Wnt-2 antibody is confirmed by downregulation of cytosolic beta-catenin and reduction in TCF-dependent transcriptional activity (TOPFLASH assay). In addition, Wnt-2-specific small interfering RNA (siRNA) treatment in the NSCLC cell line A549 also downregulated cytosolic beta-catenin and induced apoptosis. Moreover, downregulation of an inhibitor of apoptosis family protein, Survivin, was noticed both in the Wnt-2 antibody- and siRNA-treated NSCLC cells, suggesting that inhibition of Wnt-2-mediated signaling induces apoptosis through inactivating Survinin.

Antibodies, Monoclonal↗

PubMed2004

An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth.

Activation of the Wnt/beta-catenin signaling pathway has been associated with human cancers. To test whether Wnt-2 signal is a survival factor in human melanoma cells and thus represents a potential therapeutic target, we investigated the effects of inhibition of Wnt-2 signaling in human melanoma cell lines. We have developed a novel monoclonal antibody against the NH(2) terminus of the human Wnt-2 ligand that induces apoptosis in human melanoma cells overexpressing Wnt-2. Whereas incubation of this antibody with normal cells lacking Wnt-2 expression does not induce apoptosis, Wnt-2 signaling blockade by the ligand-binding antibody is confirmed by down-regulation of Dishevelled and beta-catenin. Wnt-2 small interfering RNA treatment in these cells yielded similar apoptotic effects and downstream changes. Down-regulation of an inhibitor of apoptosis family protein, survivin, was observed in both the Wnt-2 antibody-treated and small interfering RNA-treated melanoma cell lines, suggesting that the antibody induces apoptosis by inactivating survivin. In an in vivo study, this monoclonal anti-Wnt-2 antibody suppresses tumor growth in a xenograft model. These findings suggest that the anti-Wnt-2 monoclonal antibody may be useful for the treatment of patients with malignant melanoma.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer.

Aberrant activation of the Wingless-type (Wnt) signaling pathway is associated with a variety of human cancers, and we recently reported the importance of aberrant Wnt signaling in lung cancer. On the other hand, inhibition of Wnt signaling suppresses growth in numerous cell types. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that can bind Wnt in the extracellular space and inhibit Wnt signaling. Recently, down-regulation of WIF-1 has been reported in several human cancers. To discover the mechanism of WIF-1 silencing in lung cancer, we first identified the human WIF-1 promoter and subsequently examined the methylation status in the CpG islands. By using methylation-specific PCR and sequence analysis after bisulfite treatment, we demonstrate here frequent CpG island hypermethylation in the functional WIF-1 promoter region. This hypermethylation correlates with its transcriptional silencing in human lung cancer cell lines. Moreover, treatment with 5-aza-2'-deoxycytidine restores WIF-1 expression. We then studied WIF-1 expression in 18 freshly resected lung cancers, and we show a down-regulation in 15 of them (83%). This silencing also correlates with WIF-1 promoter methylation. Our results suggest that methylation silencing of WIF-1 is a common and likely important mechanism of aberrant activation of the Wnt signaling pathway in lung cancer pathogenesis, raising its therapeutic interest.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Inhibition of Wnt-1 signaling induces apoptosis in beta-catenin-deficient mesothelioma cells.

It is known that Wnt-1 signaling inhibits apoptosis by activating beta-catenin/tcf-mediated transcription. Here, we show that blocking Wnt-1 signaling in beta-catenin-deficient mesothelioma cell lines H28 and MS-1 induces apoptotic cell death. Both Wnt-1 small interfering RNA (siRNA) and Dishevelled siRNA induced significant apoptosis in these cell lines. A small molecule inhibitor of c-Jun NH(2)-terminal kinase inhibited the apoptotic cell killing induced by either Wnt-1 siRNA or Dishevelled siRNA in these cells. Our data suggest that beta-catenin-independent noncanonical pathway(s), i.e., Wnt/JNK pathway, may play a role in the apoptotic inhibition caused by Wnt-1 signaling.

Apoptosis↗

PubMed2004

Conserved cysteine-rich domain of paramyxovirus simian virus 5 V protein plays an important role in blocking apoptosis.

The paramyxovirus family includes many well-known human and animal pathogens as well as emerging viruses such as Hendra virus and Nipah virus. The V protein of simian virus 5 (SV5), a prototype of the paramyxoviruses, contains a cysteine-rich C-terminal domain which is conserved among all paramyxovirus V proteins. The V protein can block both interferon (IFN) signaling by causing degradation of STAT1 and IFN production by blocking IRF-3 nuclear import. Previously, it was reported that recombinant SV5 lacking the C terminus of the V protein (rSV5VDeltaC) induces a severe cytopathic effect (CPE) in tissue culture whereas wild-type (wt) SV5 infection does not induce CPE. In this study, the nature of the CPE and the mechanism of the induction of CPE were investigated. Through the use of DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and propidium iodide staining assays, it was shown that rSV5VDeltaC induced apoptosis. Expression of wt V protein prevented apoptosis induced by rSV5VDeltaC, suggesting that the V protein has an antiapoptotic function. Interestingly, rSV5VDeltaC induced apoptosis in U3A cells (a STAT1-deficient cell line) and in the presence of neutralizing antibody against IFN, suggesting that the induction of apoptosis by rSV5VDeltaC was independent of IFN and IFN-signaling pathways. Apoptosis induced by rSV5VDeltaC was blocked by a general caspase inhibitor, Z-VAD-FMK, but not by specific inhibitors against caspases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13, suggesting that rSV5VDeltaC-induced apoptosis can occur in a caspase 12-dependent manner. Endoplasmic reticulum stress can lead to activation of caspase 12; compared to the results seen with mock and wt SV5 infection, rSV5VDeltaC infection induced ER stress, as demonstrated by increased expression levels of known ER stress indicators GRP 78, GRP 94, and GADD153. These data suggest that rSV5VDeltaC can trigger cell death by inducing ER stress.

Animals↗

PubMed2004

Future directions: oncolytic viruses.

Oncolytic viruses offer a promising new modality for cancer treatment. The strategy of this therapy is to develop viruses capable of selectively infecting and replicating in malignant tumor cells. Oncolytic viruses can spread and destroy malignant tumors without deleterious effects in normal tissues. These viruses are genetically engineered based on both the biology of replicating viruses and the major genetic defects in human cancer cells, so that they can replicate in cancer cells but not in normal cells. The key to the development of such viruses is the identification of viral genes, the deletion or modification of which enables tumor-specific cell destruction. Several clinical trials have demonstrated the safety of oncolytic viruses as cancer therapy and have also shown some encouraging results. Much evidence suggests that oncolytic viral therapy works in synergy with standard cancer therapies. In this review, we will focus on the oncolytic viruses that may be beneficial to patients with lung cancer in the near future.

Genetic Therapy↗

PubMed2004

Activity of the suppressor of cytokine signaling-3 promoter in human non-small-cell lung cancer.

The Janus kinase (JAKs)/signal transducers and activators of transcription (STAT) signaling pathway is controlled by a classical feedback loop through suppressors of cytokine signaling (SOCS/JAB/SSI). Suppressors of cytokine signaling proteins are induced rapidly by activated STATs upon phosphorylation and act to block the cytokine signal. Abnormalities of the JAK/STAT pathway are associated with cancer. Recently, we cloned the functional 5' promoter region of the human SOCS-3 gene and showed that this region is highly conserved in murine and rat SOCS-3 promoters. In addition, we found that the wild type SOCS-3 promoter construct has significantly greater activity in human non-small-cell lung cancer (NSCLC) cell lines than in normal cells in accordance with STAT3 deregulation in these cells. Furthermore, we have confirmed that frequent hypermethylation of the functional SOCS-3 promoter correlates with its transcription silencing in NSCLC cell lines and primary lung cancer tissue samples. Restoration of SOCS-3 in lung cancer cells in which SOCS-3 has been methylation-silenced induces apoptosis and suppresses growth. Therefore, methylation silencing of SOCS-3 may be used as a marker for early detection of NSCLC. Suppressor of cytokine signaling-3 therapy may be useful for the treatment of lung cancer.

Animals↗

PubMed2003

SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer.

Lung cancer is the leading cause of cancer death in the world, but the molecular mechanisms for its development have not been well characterized. The suppressors of cytokine signaling (SOCS) are inhibitors of cytokine signaling that function via the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Eight SOCS proteins with similar structures have been identified so far. SOCS family members, however, have distinct mechanisms of inhibition of JAK/STAT signaling. Abnormalities of the JAK/STAT pathway are associated with cancer. Inhibition of signaling results in growth suppression in various cell types. Recently, the involvement of SOCS-1 in carcinogenesis has been reported. Here, we report identification of frequent hypermethylation in CpG islands of the functional SOCS-3 promoter that correlates with its transcription silencing in cell lines (lung cancer, breast cancer, and mesothelioma) and primary lung cancer tissue samples. Restoration of SOCS-3 in lung cancer cells where SOCS-3 was methylation-silenced resulted in the down-regulation of active STAT3, induction of apoptosis, and growth suppression. Our results suggest that methylation silencing of SOCS-3 is one of the important mechanisms of constitutive activation of the JAK/STAT pathway in cancer pathogenesis. The data also suggest that SOCS-3 therapy may be useful in the treatment of cancer.

Apoptosis↗

PubMed2003

Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression.

Non small cell lung cancer (NSCLC) is the leading cause of cancer deaths in the United States and worldwide. Unfortunately, standard therapies remain inadequate. An increased understanding of the molecular biology of lung cancer biology is required to develop more effective new therapies. In this report, we show that the Wnt pathway is activated through Dishevelled (Dvl) overexpression in NSCLC. Analysis of freshly resected tumors and lung cancer cell lines demonstrate that Dvl-3, a critical mediator of Wnt signaling, is overexpressed. Specifically, Dvl-3 was overexpressed significantly in 75% of fresh NSCLC microdissected samples compared to control paired matched normal lung samples. To evaluate the biological significance of Wnt signaling and, in particular, Dvl function in lung cancer, we transfected siRNA (designed to inhibit selectively human Dvl-1, -2, and -3), to the NSCLC cell line H1703, which is known to have beta-catenin-mediated Tcf-dependent transcriptional activity. Here, we demonstrate that Dvl-specific siRNA treatment in H1703 decreases significantly Dvl and beta-catenin expression, resulting in reduction of Tcf-dependent transcriptional activity, and, importantly, growth inhibition. Taken together, these data support the novel hypothesis that Dvl overexpression is critical to Wnt signaling activation and cell growth in NSCLC.

Adenocarcinoma↗

PubMed2003

Wnt pathway activation in mesothelioma: evidence of Dishevelled overexpression and transcriptional activity of beta-catenin.

Malignant pleural mesothelioma is a relatively uncommon and yet incurable tumor. The pathogenesis of mesothelioma remains poorly understood. This study evaluated the role of Wnt signaling in mesothelioma. Western blot analysis was conducted to confirm the expression of Dishevelled (Dvl) and cytosolic beta-catenin in matched autologous tissue samples (tumor and normal pleura), malignant pleural effusions, and in established mesothelioma cell lines LRK1A, REN and H513. Thirteen of 15 mesotheliomas examined showed consistent overexpression of Dvl and increased cytosolic beta-catenin levels as compared with controls. To evaluate T-cell factor (Tcf)-dependent transcriptional activity of beta-catenin, luciferase assays were conducted. Fresh mesothelioma cells (effusion derived), as well as LRK1A, REN, and H513 cell lines showed a significant fold increase (1.5-2.4-fold, P < 0.01) in Tcf-dependent transcriptional activity of beta-catenin. To evaluate the biological significance of Dvl function in mesothelioma, a PDZ domain deletion mutant (DeltaPDZ-Dvl) was created and stably transfected into LRK1A, REN, and H513. The effect of DeltaPDZ-Dvl on mesothelioma growth was assayed in vitro (colony formation assay in soft agar) and in vivo (s.c. implantation in athymic mice NCRNU-M). In mesothelioma cells tested, DeltaPDZ-Dvl-mediated inhibition of Dvl decreased cytosolic beta-catenin levels, diminished Tcf-mediated transcription, and suppressed tumorigenesis of LRK1A and REN in vitro and in vivo. DeltaPDZ-Dvl also down-regulated expression of c-myc in REN and COX-2 in H513. Our data suggest that in malignant pleural mesothelioma, Wnt signaling is activated through Dvl overexpression and downstream signaling through beta-catenin. Inhibition of this signaling leads to significant antitumor effects. These results demonstrate Dvl overexpression in human cancer and, specifically, that Wnt signaling plays a role in mesothelioma pathogenesis. These data offer possible new avenues for therapeutic intervention.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Cloning and characterization of a functional promoter of the human SOCS-3 gene.

SOCS-3 is a member of a newly discovered protein family that inhibits LIF-activated Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling in a negative auto-regulatory manner. In this study, we have cloned and characterized the promoter region of the human SOCS-3 gene. This region is approximately 1.1 kbp in length and consists of two putative STAT-binding elements, a G-rich element, and a putative TATA box. These elements are highly conserved in both murine and rat SOCS-3 promoters. Functional analysis of this region shows that the whole fragment (approximately 1.1 kbp) has high basal promoter activity and is responsive to growth factors. We also found that the wild type SOCS-3 promoter construct has significantly greater activity in non-small-cell lung cancer cell lines than in normal cells in accordance with STAT3 disregulation in these cells. Cloning of the human SOCS-3 promoter should help uncover mechanisms of regulation of the JAK-STAT pathway in human cancer.

Animals↗

PubMed2003

Induction of apoptosis by paramyxovirus simian virus 5 lacking a small hydrophobic gene.

Simian virus 5 (SV5) is a member of the paramyxovirus family, which includes emerging viruses such as Hendra virus and Nipah virus as well as many important human and animal pathogens that have been known for years. SV5 encodes eight known viral proteins, including a small hydrophobic integral membrane protein (SH) of 44 amino acids. SV5 without the SH gene (rSV5deltaSH) is viable, and growth of rSV5deltaSH in tissue culture cells and viral protein and mRNA production in rSV5deltaSH-infected cells are indistinguishable from those of the wild-type SV5 virus. However, rSV5deltaSH causes increased cytopathic effect (CPE) and apoptosis in MDBK cells and is attenuated in vivo, suggesting the SH protein plays an important role in SV5 pathogenesis. How rSV5deltaSH induces apoptosis in infected cells has been examined in this report. Tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, was detected in culture media of rSV5deltaSH-infected cells. Apoptosis induced by rSV5deltaSH was inhibited by neutralizing antibodies against TNF-alpha and TNF-alpha receptor 1 (TNF-R1), suggesting that TNF-alpha played an essential role in rSV5deltaSH-induced apoptosis in a TNF-R1-dependent manner. Examination of important proteins in the TNF-alpha signaling pathway showed that p65, a major NF-kappaB subunit whose activation can lead to transcription of TNF-alpha, was first translocated to the nucleus and was capable of binding to DNA and then was targeted for degradation in rSV5deltaSH-infected cells while expression levels of TNF-R1 remained relatively constant. Thus, rSV5deltaSH induced cell death by activating TNF-alpha expression, possibly through activation of the NF-kappaB subunit p65 and then targeting p65 for degradation, leading to apoptosis.

Animals↗

PubMed2002

The V proteins of simian virus 5 and other paramyxoviruses inhibit induction of interferon-beta.

In this article we show that the paramyxovirus SV5 is a poor inducer of interferon-beta (IFN-beta). This inefficient induction is a consequence of the expression of an intact viral V protein. In the absence of the viral V protein cysteine-rich C-terminal domain, IFN-beta mRNA is strongly induced and the transcription factors NF-kappaB and IRF-3 are activated significantly. The V protein can work in isolation from SV5 to block intracellular dsRNA signaling. The mechanism of block to dsRNA signaling is distinct from that previously observed for blocking IFN signaling in that proteolysis of candidate factors cannot be detected, and furthermore, the respective blocks require distinct protein domains. Blocking of the induction of IFN-beta by dsRNA requires the C-terminal cysteine-rich domain, a feature that is highly conserved among paramyxoviruses. We demonstrate that the V proteins from other paramyxoviruses have equivalent functions and speculate that limiting the yield of IFN-beta during infection may be a general property of paramyxoviruses.

Animals↗

PubMed2002

Recovery of paramyxovirus simian virus 5 with a V protein lacking the conserved cysteine-rich domain: the multifunctional V protein blocks both interferon-beta induction and interferon signaling.

The V protein of the Paramyxovirus simian virus 5 (SV5) is a multifunctional protein containing an N-terminal 164 residue domain that is shared with the P protein and a distinct C-terminal domain that is cysteine-rich and which is highly conserved among Paramyxoviruses. We report the recovery from Vero cells [interferon (IFN) nonproducing cells] of a recombinant SV5 (rSV5) that lacks the V protein C-terminal specific domain (rSV5VDeltaC). In Vero cells rSV5VDeltaC forms large plaques and grows at a rate and titer similar to those of rSV5. In BHK or CV-1 cells rSV5VDeltaC forms small plaques and grows poorly. However, even when grown in Vero cells rSV5VDeltaC reverts to pseudo-wild-type virus in four to five passages, indicating the importance of the V protein for successful replication of SV5. Whereas rSV5 grows in many cell types with minimal cytopathic effect (CPE), rSV5VDeltaC causes extensive CPE in the same cell types. To overcome the antiviral state induced by IFN, many viruses have evolved mechanisms to counteract the effects of IFN by blocking the production of IFN and abrogating IFN signaling. Whereas rSV5 blocks IFN signaling by mediating the degradation of STAT1, rSV5VDeltaC does not cause the degradation of STAT1 and IFN signaling occurs through formation of the ISGF3 transcription complex. Furthermore, we find that rSV5 infection of cells prevents production of IFN-beta. The transcription factor IRF-3 which is required for transcription of the IFN-beta gene is not translocated from the cytoplasm to the nucleus in rSV5-infected cells. In contrast, in rSV5VDeltaC-infected cells IRF-3 is localized predominantly in the nucleus and IFN-beta is produced. By using ectopic expression of IRF-3, it was shown that after dsRNA treatment and expression of the V protein IRF-3 remained in the cytoplasm, whereas after dsRNA treatment and expression of the P protein (which lacks the C-terminal cysteine-rich domain) IRF-3 was localized predominantly in the nucleus. Thus, SV5 blocks two distinct pathways of the innate immune response, both of which require the presence of the C-terminal specific cysteine-rich domain of the multifunctional SV5 V protein.

Amino Acid Sequence↗

PubMed2002

The growth of Drosophila bristles and laterals is not restricted to the tip or base.

The highly elongated bristles of Drosophila have proven to be a valuable model system for studying cellular morphogenesis. Extending bristles contain a series of large bundles of actin filaments juxtaposed to the plasma membrane and centrally located microtubules. Models to explain the extension of the bristle have principally focused on the assembly of actin filaments at the distal tip of the bristle. We have used time-lapse observations of wild-type and mutant bristles and the related arista laterals and come to the conclusion that growth takes place throughout the growing cellular extension. This distributed growth can explain the behavior of split laterals and the shape changes seen at the tip during bristle and lateral outgrowth. Inhibitor studies suggest that the microtubule cytoskeleton is essential for maintaining the highly biased axial growth of these structures. We have used fluorescence recovery after photo-bleaching to study the dynamics of the cytoskeleton during bristle growth. Our experiments show that actin bundles in growing bristles are quite stable and move in a retrograde fashion. The bristle microtubules are less stable. The retrograde movement of the peripheral actin appears to be counterbalanced by the distally directed movement of cytoplasm in the center of the bristle.

Actin Cytoskeleton↗

PubMed2002

The frizzled pathway regulates the development of arista laterals.

BACKGROUND: The frizzled pathway in Drosophila has been studied intensively for its role in the development of planar polarity in wing hairs, thoracic bristles and ommatidia. Selected cells in the arista (the terminal segment of the antenna) elaborate a lateral projection that shares characteristics with both hairs and bristles. RESULTS: We found that mutations in putative downstream members of the frizzled pathway, such as inturned resulted in multipled and split laterals, but no obvious polarity defects. Mutations in upstream genes such as frizzled did not show an adult arista phenotype. When we examined lateral development in the mutants we found that, as is the case on the wing for hair development the frizzled pathway regulated the subcellular location for lateral initiation. However, on the arista an altered location for lateral initiation did not result in altered polarity, as did an altered site for hair initiation. The regulation of lateral development involved the preferential accumulation of Frizzled protein at the distal edges of lateral cells much as is seen on the wing. In contrast to the situation in wing cells, in arista cells the location for lateral initiation was close to but did not overlap the region of preferential Frizzled accumulation. CONCLUSION: Our data indicates that a modified version of the frizzled pathway regulates arista development. We conclude that the lack of a polarity defect in mutant aristae is likely to be a consequence of inherent differences in the cell biology of wing hair and lateral forming cells.

Animals↗

PubMed2002

The genetic control of arista lateral morphogenesis in Drosophila.

The sensory bristles and epidermal hairs of Drosophila have proven to be valuable model cell types for studying the role of the cytoskeleton in cellular morphogenesis. We have recently begun to use the arista laterals as a third model cell type. The laterals display a combination of bristle and hair characteristics and provide a system where we can compare the relative importance of specific genes and subcellular structures for the morphogenesis of different polarized cellular extensions. We have characterized the lateral phenotype of a collection of mutations selected because of their phenotypes in hairs and bristles. In many but not all ways the lateral phenotypes are similar to the hair and bristle phenotypes. We provide compelling genetic evidence for the importance of the actin cytoskeleton in lateral elongation, shaping and integrity. Our observations provide evidence that defects in actin bundling can destabilize laterals so that they split during growth. Temperature shift experiments suggest that a defect in lateral initiation can lead to subsequent splitting. These observations provide a link between multiple hair and lateral cells forming by both multiple initiation events and by the splitting of individual cellular extensions. We also found that mutations that lead to lateral splitting typically alter the stereotypic arrangement of actin filament bundles and microtubules in laterals.

Actins↗