Atypical Smooth Muscle Cells Research Articles

Retroperitoneal Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]) is a rare disease of unknown etiology, which almost exclusively affects women of child-bearing age. The disease is characterized histologically by diffuse hamartomatous proliferation of atypical smooth muscle cells in the lung, lymphatic trunk, and lymph nodes and causes gradual obstruction of small airways, lymphatic vessels, and vasculature. 1 The primary target of LAM is the chest, and most previous reports of LAM have concentrated on the pulmonary findings. However, extrapulmonary LAM rarely occurs with or without subsequent involvement of the lung, and several cases of extra-pulmonary LAM involving abdominal or pelvic retroperitoneal organs have been reported in the radiology literature. 2-7 We describe a case of histologically proven retroperitoneal LAM in a female patient with sonography, computed tomography (CT), gadolinium-enhanced magnetic resonance imaging (MRI), and positron emission tomography (PET).

Spontaneous electrical and Ca2+ signals in the mouse renal pelvis that drive pyeloureteric peristalsis

1. Peristalsis in the smooth muscle cell (SMC) wall of the pyeloureteric system is unique in physiology in that the primary pacemaker resides in a population of atypical SMCs situated near the border of the renal papilla. 2. Atypical SMCs display high-frequency Ca(2+) transients upon the spontaneous release of Ca(2+) from inositol 1,4,5-trisphosphate (IP(3))-dependent stores that trigger cation-selective spontaneous transient depolarizations (STDs). In the presence of nifedipine, these Ca(2+) transients and STDs seldom propagate > 100 mum. Synchronization of STDs in neighbouring atypical SMCs into an electrical signal that can trigger action potential discharge and contraction in the typical SMC layer involves a coupled oscillator mechanism dependent on Ca(2+) entry through L-type voltage-operated Ca(2+) channels. 3. A population of spindle- or stellate-shaped cells, immunopositive for the tyrosine receptor kinase kit, is sparsely distributed throughout the pyeloureteric system. In addition, Ca(2+) transients and action potentials of long duration occurring at low frequencies have been recorded in a population of fusiform cells, which we have termed interstitial cells of Cajal (ICC)-like cells. 4. The electrical and Ca(2+) signals in ICC-like cells are abolished upon blockade of Ca(2+) release from either IP(3)- or ryanodine-dependent Ca(2+) stores. However, the spontaneous Ca(2+) signals in atypical SMCs or ICC-like cells are little affected in W/W(-v) transgenic mice, which have extensive lesions of their intestinal ICC networks. 5. In summary, we have developed a model of pyeloureteric pacemaking in which atypical SMCs are indeed the primary pacemakers, but the function of ICC-like cells has yet to be determined.

Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis

We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene-related peptide (CGRP). Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs and ATSMCs) within the renal pelvis wall were recorded separately using tension and intracellular microelectrode recording techniques and Fluo-4 Ca2+ imaging. Immunohistochemical and electron microscopic studies were also carried out. Bundles of CGRP containing transient receptor potential cation channel, subfamily V, member 1-positive sensory nerves were situated near both TSMCs and ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and duration of spontaneous phasic contractions, action potentials and Ca2+ transients in TSMCs. CGRP and agents increasing internal cyclic adenosine monophosphate (cAMP) mimicked the nerve-mediated modulation of TSMC activity and suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or cAMP stimulators was blocked by glibenclamide, while their negative chronotropic effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but inhibited ATSMC Ca2+ transients, while both 5-hydroxydecanoate and diazoxide, a blocker and opener of mitochondrial ATP-sensitive K+ channels, respectively, reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous excitation of TSMCs. The negative chronotropic effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather than opening of plasmalemmal ATP-sensitive K+ channels in TSMCs. The positive inotropic effects of CGRP may derive from activation of TSMC L-type Ca2+ channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in generating Ca2+ transients.

Physiology, Injury, and Recovery of Interstitial Cells of Cajal: Basic and Clinical Science

In the last 15 years, our understanding of the cellular basis of gastrointestinal function has been altered irreversibly by the discovery that normal gastrointestinal (GI) motility requires interstitial cells of Cajal (ICC). Research in this relatively short time period has modified our original concept that the core unit that controls motility is made up of nerves and smooth muscle, to one that now includes ICC. This concept has now expanded to beyond the GI tract, suggesting that it may be a fundamental property of the regulation of smooth muscle function that requires rhythmic contraction. ICC are distributed throughout the GI tract, have important functions in the control of GI motility, and are often abnormal in diseased states. Recently, significant steps forward have been made in our understanding of the physiology of ICC as well as mechanisms of injury and recovery. These advances are the focus of this review. The Physiology of ICC Unique motor patterns are intrinsic to every organ of the GI tract, which suit their functions related to mixing, absorption, and anally directed movement. The ICC are an integral part of the control of these motor activities. The distribution of ICC throughout the musculature is associated with nerve structures. Myenteric pacemaker ICC surround the myenteric or Auerbach’s plexus and intramuscular ICC are associated with nerve varicosities throughout the muscle layers (Figures 1 and 2). Other subpopulations of ICC are associated with nonganglionated plexuses of nerve varicosities at the inner borders of the circular muscle layers in the intestine and colon (Figures 1 and 2). The best understood function is that of pacemaker activity in the stomach and small intestine where the ICC generate a periodic depolarization at a characteristic frequency in each of these organs that is called the slow wave or pacemaker activity.

Lymphangioleiomyomatosis: A Case Report

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown cause that traditionally affects young women of reproductive age. It is characterized by a proliferation of atypical smooth muscle cells, preferentially along the bronchovascular structures, that causes progressive respiratory failure. LAM is almost universally fatal without a lung transplant, although new clinical trials are ongoing. Because of its rareness and nonspecific presenting symptoms, patients often receive a missed or delayed diagnosis. We present the case of a 51-year-old postmenopausal woman who had hemoptysis ultimately determined to be due to LAM. As is common for patients with LAM, the initial chest radiograph was unremarkable, whereas subsequent computed tomography (CT) demonstrated the distinctive pulmonary parenchymal cysts. Biopsy of an HMB-45-positive, para-aortic lymphangiomyoma provided further confirmation of the diagnosis. LAM may be more common than previously recognized, and it is imperative for primary care providers to be able to recognize this disease so they can make prompt referrals to appropriate specialty centers.

Smooth muscle cell calcium activation mechanisms

Smooth muscle cell (SMC) contraction is controlled by the Ca2+ and Rho kinase signalling pathways. While the SMC Rho kinase system seems to be reasonably constant, there is enormous variation with regard to the mechanisms responsible for generating Ca2+ signals. One way of dealing with this diversity is to consider how this system has been adapted to control different SMC functions. Phasic SMCs (vas deferens, uterus and bladder) rely on membrane depolarization to drive Ca2+ influx across the plasma membrane. This depolarization can be induced by neurotransmitters or through the operation of a membrane oscillator. Many tonic SMCs (vascular, airway and corpus cavernosum) are driven by a cytosolic Ca2+ oscillator that generates periodic pulses of Ca2+. A similar oscillator is present in pacemaker cells such as the interstitial cells of Cajal (ICCs) and atypical SMCs that control other tonic SMCs (gastrointestinal, urethra, ureter). The changes in membrane potential induced by these cytosolic oscillators does not drive contraction directly but it functions to couple together individual oscillators to provide the synchronization that is a characteristic feature of many tonic SMCs.

Urinary Bladder Leiomyoma Associated with Pulmonary Lymphangioleiomyomatosis

Leiomyomas account for less than 0.43% of all bladder tumors. To date only about 250 cases have been reported in the literature. Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease featuring abnormal proliferation of atypical smooth muscle cells around bronchovascular structures. We describe a woman with LAM who presented with pelvic pain and was found to have a leiomyoma of the bladder wall. Although urologic manifestations of pulmonary LAM are uncommon, they should be considered in the differential diagnosis of a patient who presents with a pelvic mass and a history of LAM.

Role of Ca2+ entry and Ca2+ stores in atypical smooth muscle cell autorhythmicity in the mouse renal pelvis

Electrically active atypical smooth muscle cells (ASMCs) within the renal pelvis have long been considered to act as pacemaker cells driving pelviureteric peristalsis. We have investigated the role of Ca2+ entry and uptake into and release from internal stores in the generation of Ca2+ transients and spontaneous transient depolarizations (STDs) in ASMCs. The electrical activity and separately visualized changes in intracellular Ca2+ concentration in typical smooth muscle cells (TSMCs), ASMCs and interstitial cells of Cajal-like cells (ICC-LCs) were recorded using intracellular microelectrodes and a fluorescent Ca2+ indicator, fluo-4. In 1 microM nifedipine, high frequency (10-30 min(-1)) Ca2+ transients and STDs were recorded in ASMCs, while ICC-LCs displayed low frequency (1-3 min(-1)) Ca2+ transients. All spontaneous electrical activity and Ca2+ transients were blocked upon removal of Ca2+ from the bathing solution, blockade of Ca2+ store uptake with cyclopiazonic acid (CPA) and with 2-aminoethoxy-diphenylborate (2-APB). STD amplitudes were reduced upon removal of the extracellular Na+ or blockade of IP3 dependent Ca2+ store release with neomycin or U73122. Blockade of ryanodine-sensitive Ca2+ release blocked ICC-LC Ca2+ transients but only reduced Ca2+ transient discharge in ASMCs. STDs in ASMCS were also little affected by DIDS, La3+, Gd3+ or by the replacement of extracellular Cl(-) with isethionate. ASMCs generated Ca2+ transients and cation-selective STDs via mechanisms involving Ca2+ release from IP3-dependent Ca2+ stores, STD stimulation of TSMCs was supported by Ca2+ entry through L type Ca2+ channels and Ca2+ release from ryanodine-sensitive stores.

Spontaneous electrical and Ca2+ signals in typical and atypical smooth muscle cells and interstitial cell of Cajal‐like cells of mouse renal pelvis

Electrical rhythmicity in the renal pelvis provides the fundamental drive for the peristaltic contractions that propel urine from the kidney to bladder for storage until micturition. Although atypical smooth muscles (ASMCs) within the most proximal regions of the renal pelvis have long been implicated as the pacemaker cells, the presence of a sparsely distributed population of rhythmically active Kit-positive interstitial cells of Cajal-like cells (ICC-LCs) have confounded our understanding of pelviureteric peristalsis. We have recorded the electrical activity and separately visualized changes in intracellular Ca(2+) concentration in typical smooth muscle cells (TSMCs), ASMCs and ICC-LCs using intracellular microelectrodes and a fluorescent Ca(2+) indicator, fluo-4. Nifedipine (1-10 microm)-sensitive driven action potentials and Ca(2+) waves (frequency 6-15 min(-1)) propagated through the TSMC layer at a velocity of 1-2 mm s(-1). High frequency (10-40 min(-1)) Ca(2+) transients and spontaneous transient depolarizations (STDs) were recorded in ASMCs in the absence or presence of 1 microm nifedipine. ICC-LCs displayed low frequency (1-3 min(-1)) Ca(2+) transients which we speculated arose from cells that displayed action potentials with long plateaus (2-5 s). Neither electrical activity propagated over distances > 50 microm. In 1 microm nifedipine, ASMCs or ICC-LCs separated by < 30 microm displayed some synchronicity in their Ca(2+) transient discharge suggesting that they may well be acting as 'point sources' of excitation to the TSMC layer. We speculate that ASMCs act as the primary pacemaker in the renal pelvis while ICC-LCs play a supportive role, but can take over pacemaking in the absence of the proximal pacemaker drive.

A Case of Lymphangioleiomyomatosis Presenting as a Lung Mass

Lymphangioleiomyomatosis (LAM) is a rare disease that affects females of reproductive age. It is characterized by the abnormal proliferation of smooth muscle cells in the lung and along the axial lymphatics. We report a case of lymphangioleiomyomatosis presenting as a lung mass. The patient visited the emergency room because of dyspnea upon exertion. The chest X-ray showed a lung mass in the right lower lung field and a pneumothorax in the left lung. Chest computed tomography revealed a sized mass in the right lower lobe and multiple thin-walled small cysts scattered in both lungs. Transbronchial biopsy of the lung mass was performed. The biopsy specimen showed atypical smooth muscle cell proliferation and cystic dilatation of the terminal bronchioles, which confirmed the diagnosis of lymphangioleiomyomatosis. To the best of our knowledge, this is the first case of lymphangioleiomyomatosis presenting as a lung mass.

Pyeloureteric peristalsis: role of atypical smooth muscle cells and interstitial cells of Cajal‐like cells as pacemakers

Pyeloureteric peristalsis has long been considered to be triggered by pacemaker atypical smooth muscle cells (SMC) located in the proximal regions of the renal pelvis. However, interstitial cells with many of the morphological features and c-Kit immuno-reactivity of interstitial cells of Cajal (ICC), the established pacemaker cells in the intestine, have been demonstrated to be present in small numbers within the ureteropelvic junction (UPJ) of many mammals. Freshly isolated ICC-like cells (ICC-LC) of the mouse UPJ also display autorhyhmicity. This review discusses the notion that ureteric peristalsis depends on the presence of both atypical SMC and ICC-LC which form separate but interconnected networks that drive electrically quiescent typical SMC. In contrast to the intestine or prostate, all regenerative potential discharge in the mouse UPJ is abolished by the L-type Ca(2+) channel blocker nifedipine revealing a fundamental pacemaker signal. Whether these pacemaker transients arise from atypical SMC or ICC-LC or both has yet to be established. We speculate that the presence of spontaneously active ICC-LC in the distal regions of the UPJ maintains rudimentary peristaltic waves and movement of urine towards the bladder after pyeloureteral obstruction or pyeloplasty and disconnection from the proximal pacemaker drive.

Involvement of interstitial cells of Cajal in the control of smooth muscle excitability

Involvement of interstitial cells of Cajal in the control of smooth muscle excitability

Organization and function of ICC in the urinary tract

ICC are found in both the upper and lower urinary tract. They are not found in the ureter itself but are confined to the lamina propria of the renal pelvis and pelvi-calyceal junction. They do not appear to have a primary pacemaker role (this is ascribed to atypical smooth muscle cells in the same location) but rather conduct and amplify the pacemaker signals generated by the atypical smooth muscle cells. In the bladder, ICC are widely distributed in the sub-urothelial region, in the lamina propria and at the margins of the detrusor smooth muscle bundles. Again they appear not to have a pacemaking role and such evidence as there is would suggest that they have a role in the modulation of signal transduction. The strongest evidence that ICC in the urinary tract act as pacemakers comes from studies of those in the urethra. Isolated ICC show regular spontaneous depolarizations in current clamp which resemble very closely the slow waves recorded from intact tissue. In voltage clamp they show abundant calcium-activated chloride current and spontaneous transient inward currents which can be blocked by chloride channel blockers. However, their role in the modulation of urethral tone has yet to be fully elucidated.

Linfangioleiomiomatose: A propósito de um caso clínico

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown etiology affecting woman, primarily in their reproductive years. It is characterized by non-neoplasic proliferation of atypical smooth muscle cells that may lead to airway, lymphatic and blood vessel obstruction over time.A nine-year followed-up case of LAM is described, which presents with some unusual details as worsening haemoptysis in the setting of pregnancy and absence of cough or pneumothorax along the course of the disease. Neither haemoptysis nor gradual pulmonary function deterioration seemed to be influenced by hormone therapy. A brief review of the disease is then presented.Rev Port Pneumol 2005; XI (6): 573-585

Interstitial cell of Cajal-like cells in the upper urinary tract.

Autorhythmicity in the upper urinary tract (UUT) has long been considered to arise in specialized atypical smooth muscle cells (SMC) predominately situated in the most proximal regions of the pyeloureteric system. These atypical SMC pacemakers have been thought to trigger adjacent electrically-quiescent typical SMC to fire action potentials which allow an influx of Ca2+ and the generation of muscle contraction. More recently, the presence of cells with many of the morphological, electrical and immunohistochemical characteristics of interstitial cells of Cajal (ICC), the pacemaker cells of the gastrointestinal tract, have been located in many regions of both the upper and lower urinary tract. This article reviews the evidence from the literature and from our laboratory supporting a role of both atypical SMC and ICC-like cells in the initiation and propagation of pyeloureteric peristalsis in the UUT. We propose a new model in which there are 2 populations of pacemaker cells, high frequency atypical SMC and lower frequency ICC-like cells, both of which can drive electrically-quiescent typical SMC. The relative presence of these 2 populations of pacemaker cells and the relatively-long refractoriness of typical SMC determines the decreasing frequency of contraction with distance from the renal fornix. In the absence of the proximal pacemaker drive from atypical SMC after pyeloureteral/ureteral obstruction or surgery, ICC-like cell pacemaking provides a compensatory mechanism allowing the ureter to maintain rudimentary peristaltic waves and movement of urine from the pyelon towards the bladder.

Tumor suppressor MDA-7/IL-24 selectively inhibits vascular smooth muscle cell growth and migration

Abnormalities in smooth muscle cell (SMC) proliferation and differentiation underlie the pathogenesis of proliferative vascular diseases. MDA-7 (HUGO approved symbol IL24) is a unique gene, originally identified as a tumor suppressor and more recently shown to have cytokine activity. MDA-7/IL24 has been implicated in apoptosis and cellular differentiation in tumor cells and in tumor invasion/metastasis in clinical specimens—properties central to SMC remodeling during proliferative vascular diseases. In this study, we evaluated the effects of overexpressing MDA-7/IL24 in various SMC: the apparently “normal” rat PAC1 cell line, primary human coronary artery SMC, and normal rat aortic SMC. We transduced SMC with adenovirus-mda7 (Ad-mda7) or control virus (Ad-Luc) and assessed cell viability, apoptosis, and migration. Ad-mda7 suppressed PAC1 cell growth in a dose-dependent manner while having no effect on normal primary human coronary artery cells or rat aortic SMC, despite strong expression of the MDA-7 transgene in all SMC. Similarly, Ad-mda7 treatment induced apoptosis in PAC1 cells with essentially no effect on normal coronary and rat aortic SMC. Ad-mda7 also inhibited serum-stimulated PAC1 cell migration. Karyotype analysis of PAC1 cells revealed that they exhibit multiple chromosomal aberrations. Importantly, recombinant MDA-7 did not elicit cell death or STAT-3 activation in PAC1 SMC, suggesting that the effects of Ad-mda7 were mediated through an intracellular pathway. These data demonstrate that Ad-mda7 exhibits selectivity in apoptosis induction and growth suppression in an atypical SMC line, raising new questions pertaining to heterogeneity in SMC death susceptibility.

Pyeloureteral motility and ureteral peristalsis: essential role of sensory nerves and endogenous prostaglandins.

The cellular mechanisms that underlie the initiation and propagation of the peristaltic contractions, which transport urine from the kidney to the bladder for storage, remain little understood. Extracellular and intracellular microelectrode recordings have identified two populations of smooth muscle cells as well as a population of renal interstitial cells (RICs) that all display spontaneous electrical activity. By analogy with the heart it has been proposed that atypical smooth muscle cells, preferentially located in the very proximal regions of the renal pelvis, generate the essential pacemaker signal. These pacemaker potentials propagate to neighbouring typical smooth muscle cells or RICs to trigger action potential discharge. These action potentials then propagate distally to trigger other bundles of typical smooth muscle cells. The frequency of action potential discharge and contraction decreases as the relative number of RICs and atypical smooth muscle cells compared to typical smooth muscle cells decreases with distance from the renal fornix. It is clear that functional capsaicin-sensitive sensory afferents and the endogenous release of both tachykinins and prostaglandins are essential in the maintenance of normal peristalsis, as well as in monitoring and responding to any chemical or mechanical stimulation. However, the cellular mechanisms underlying the action of these endogenously-released agents remain to be elucidated.

Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare disease categorized by an overgrowth of atypical smooth muscle cells (LAM cells) in the lungs and axial lymphatics, which is associated with the mesenchymal tumor angiomyolipoma. The disease occurs in women generally in their mid thirties with a prevalence approximately 1 per million in the general population but is much more frequent in women with tuberous sclerosis complex (TSC). LAM is categorized by airflow obstruction, lung cysts, recurrent pneumothorax, and pleural and abdominal chylous collections. The disease is progressive, generally resulting in respiratory failure and death. The TSC-2 gene is abnormal in LAM cells and may be responsible for their disordered growth. These cells are of an unusual phenotype, expressing smooth muscle proteins, melanoma proteins, estrogen and progesterone receptors. Although at present of unknown significance these are useful in diagnosis. Treatment is largely supportive, being directed at airflow obstruction, pneumothorax, chylous complications, and bleeding from angiomyolipomas. In patients with rapidly progressive disease, hormone manipulation is frequently tried in the form of progesterone or antiestrogen therapies although no firm evidence of their efficacy exists.

CHARACTERIZATION OF THE SPONTANEOUS ELECTRICAL AND CONTRACTILE ACTIVITY OF SMOOTH MUSCLE CELLS IN THE RAT UPPER URINARY TRACT

We morphologically and electrophysiologically identified the cells that generate the electrical activity underlying the peristaltic contractions of the rat upper urinary tract. Electron microscopy and tension recording techniques were used to characterize the smooth muscle cells underlying spontaneous contractions in the wall of the rat ureter, and proximal and distal renal pelvis. Intracellular microelectrodes, containing 4% neurobiotin were used to record data from the cells of the renal pelvis, which were later viewed on a confocal microscope. Spontaneous myogenic contractions (average 22.3 +/- 2.2 minutes(-1)) originated in the proximal renal pelvis and propagated into the distal renal pelvis and ureter in 6 preparations. Smooth muscle cells in the renal pelvis and ureter were typical in appearance with greater than 85% of their sectional area containing clumped contractile filaments. In contrast, contractile fibrils occupied only 65% of the sectional area of the smooth muscle cells within the most proximal region of the renal pelvis (pelvicaliceal junction). In strips of the renal pelvis spindle shaped cells 83 to 200 microm. long fired spontaneous action potentials (6 minutes(-1)) consisting of an initial spike, a quiescent plateau phase and abrupt hyperpolarization to a peak diastolic potential of -60 mV. Other spindle shaped cells 94 to 112 microm. long displayed small membrane transients (15 minutes(-1)) 9 to 19 mV. in amplitude, firing from a diastolic potential of -40 mV. It is likely that the spontaneous contractile activity of the rat upper urinary tract arises from the discharge of action potentials in typical smooth muscle cells of the proximal renal pelvis that are directly driven by the spontaneous membrane oscillations of atypical smooth muscle cells.

The three-dimensional architecture of retinal blood vessels in KK mice, with special reference to the smooth muscle cells and pericytes.

In the present study, the three-dimensional architecture of retinal vasculature was studied in KK mice, by combined use of resin injection, chemical treatment and scanning electron microscopy (SEM). In particular, Mercox/methylmethacrylate resin-injected eye tissues were subjected in sequence to NaClO immersion, ultrasonication and HCl treatment. The present technological innovation made possible SEM visualization of deeper retinal vasculature. In KK mice, the tunica media of stem arterioles and of first and second order branches consisted of a single layer of spindle-shaped smooth muscle cells provided with spine-like cytoplasmic processes. In addition, there occurred small triangular smooth muscle cells provided with slender cytoplasmic processes. The processes, giving off tiny secondary processes, overlapped with each other, thus forming assemblages around branching sites. Such a structure was particularly prominent for those branching sites where parent arterioles gave rise to their branches in a side arm-like pattern. The third (and occasionally fourth) order branches were surrounded by atypical smooth muscle cells, with considerable dimension of endothelial surface remaining uncovered. Capillary pericytes consisted of fusiform cell bodies and slender cytoplasmic processes. Smooth muscle cells of retinal venules differed from those of arterioles. They were stellate in shape, exhibiting several cytoplasmic processes.